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Human DNA Polymerase gamma Mutation Database

Human DNA polymerase is composed of two subunits, a 140 kDa catalytic subunit encoded by the POLG on chromosome 15q25, and a 55kDa accessory subunit encoded by the POLG2 gene on chromosome 17q23-24.

A number of mutations have been mapped to the gene for the catalytic subunit of DNA polymerase, POLG, and found to be associated with mitochondrial diseases.

This database lists all known mutations in the coding region of the POLG gene and describes the associated disease. This list is maintained by the Mitochondrial DNA Replication Group at NIEHS.

The nucleotide changes are numbered from the initiation Methionine codon and are based on the cDNA (accession U60325.1) and gene sequence (accession AF497906.1).

All inquiries, additions to the list, and comments should be made to Bill Copeland or Maggie Humble.

Alignment Document (132 KB)
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chart of Mutations in DNA Polymerase

Visual overview of the POLG mutations.

To search for multiple exons, hold <Ctrl> while selecting multiple options.


Amino Acid Substitution: R3P
cDNA Position: 8 g→c (exon 2)
Disease Genetics Frequency Reference
PEO ar (Van Goethem et al., 2001) reported 0 out of 229 control Individuals (<0.4%) (Van Goethem et al., 2001)
PubMed
Amino Acid Substitution: G11D
cDNA Position: 32 g→a (exon 2)
Disease Genetics Frequency Reference
Ataxia Neuropathy Found in cis with R627Q and in trans with R852C, and also found as a Heterozygous mutation with a failure to thrive (Wong et al., 2008)
PubMed
Alpers Found in cis w/ R852C and in trans w/ W748S. In a second pt. found in cis w/R852C and in trans w/ A467T. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Alpers Found in cis w/ R852C and in trans w/ A467T. In a 2nd pt., found in cis w/ R852C and in trans w/ W748S and E1143G (Stewart et al., 2009)
PubMed
Leigh Syndrome Found in cis with R852C and in trans with W748S (Naess et al., 2009)
PubMed
Multiple system atrophy Found with R852C in a 58 y.o. female with progressive cerebellar atrophy. Pt. had mtDNA deletions and mtDNA depletion. (Mehta et al., 2011)
PubMed
Seizures and liver failure Found in trans w/ A467T and in cis w/ R852C in an 8 mo. w/ seizures, liver failure, and lactic acidosis. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Encephalopathy Found in cis w/ R852C and in trans w/ R627Q in a 25 y.o. w/ dementia, encephalopathy, and stroke. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: P18S
cDNA Position: 52 t→g (exon 2)
Disease Genetics Frequency Reference
Neutral polymorphism 0.6% of 450 individuals (GeneSNPs, 2004)
PubMed
Amino Acid Substitution: S28C
cDNA Position: 82 a→t (exon 2)
Disease Genetics Frequency Reference
PEO Found in a 25 y.o. pt. that is homozygous for the W748S mutation with PEO, ataxia, ptosis, and hearing loss Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: R42X
cDNA Position: 125 del (exon 2)
Disease Genetics Frequency Reference
Reference # rs59510277
PubMed
Amino Acid Substitution: ±Gln at aa 43-52
cDNA Position: ±(CAG)n at nucleotides 126 to 157 (exon 2)
Disease Genetics Frequency Reference
Male infertility Identified an association between absence of the common, ten CAG repeat allele and male infertility due to a range of sperm quality defects. Rovio et al., 2001 reported 88% of both Finnish and ethnically mixed populations carry the predominant allele of 10 CAG repeats (Rovio et al., 2001)
PubMed
Male infertility Predictive value for infertility in a man homozygous for the POLG CAG polymorphism was 15.5% (95% CI: 4.8-51%). There was a positive association with sperm concentration. Studied in 1298 male subjects: 429 patients with infertility/subfertility, and 869 controls (495 men from the general population with unknown fertility and 374 recent fathers) (Jensen et al., 2004)
PubMed
The human DNA POL gamma is unique in that the first exon of the gene contains a CAG10 trinucleotide repeat. (Ropp and Copeland, 1996) 
PubMed
Male infertility Micro-deletion in the Y chromosome frequency in France, averaged: 10–15% in cases of azoospermia, and 5–10% in cases of oligozoospermia. (Aknin-Seifer et al., 2005)
PubMed
Male infertility Suggested that the POLG1 CAG-repeat polymorphisms does not contribute to oligozoospermia in French and Italian populations. 625 individuals in three groups of case-controls from three different Italian regions (Brusco et al., 2006)
PubMed
Male infertility 80 normozoospermic and 124 non-normozoospermic semen samples were analyzed for nucleotide substitutions. There were no significant differences in the frequencies of nucleotide substitution and POLgamma genotypes in the two groups. (Harris et al., 2006)
PubMed
Male infertility The mutated genotype was found at the same frequency in both infertile and normospermic Italian men. (Krausz et al., 2004)
PubMed
Frequency study The heterozygosity level ranges from 22% in Europe to 13.6% in Southwest Asia with the lowest value of 7.4% in Siberia/East Asia. Found an extremely low variability of the trinucleotide CAG microsatellite repeats. The population sample consisted of 1,330 individuals from 3 large geographic areas: Europe, Southwest Asia, and Siberia/East Asia. (Malyarchuk et al., 2005)
PubMed
Testicular cancer Studied CAG repeat length variation at the POLG gene locus in a group of patients with testicular tumors compared with an equivalent healthy Polish male population. The CAG repeats in the POLG gene were significantly more frequent in testicular cancer patients than in healthy men (26% versus 11%, P=0.035 by the Fisher exact test). Nowak et al., 2005 reported 11% healthy Polish men (n=55) were heterozygous, and 26% of testicular cancer patients (n=49) were heterozygous for the CAG repeats ≠ 10. With no clinical differences in tumor pathology. (Nowak et al., 2005)
PubMed
Idiopathic sporadic Parkinson Increase frequency of non-10/11 (CAG) variant in Parkinson disease (PD) Luoma, 2007: found in 10% PD patients compared with 3.5-4.3% spouse/population controls. (Luoma et al., 2007)
PubMed
Seminoma testicular cancer Homozygous lack of 10 CAG repeat 4.9% of Danish men (n=869). 96.7% of Seminoma pts. (Jensen et al., 2008)
PubMed
Friedreich's Ataxia Age of onset of FRDA is inversely correlated to the POLG CAG repeats Study done in 49 Iranian FRDA pts. (Heidari et al., 2008)
PubMed
Sporadic Parkinson CAG repeat region screened in 243 Swedish Parkinson’s pts. An assoc. was found with repeats in glutamine runs that were not 10 or 11 in number. 243 Swedish PD patients and 279 Swedish controls (Anvret, et al., 2010)
PubMed
PEO and ovarian failure Compound heterozygote found w/ K947R (Baruffini et al., 2011)
PubMed
10/11Q 10/11Q found in a Chinese population with Parkinsonism at a frequency of 86.9% compared to the controls at 93.5% and non 10/11Q runs were found at 13.1% in PD pts and 6.5% in controls. 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
This study was a meta-analysis of 13 other published works and the overall result was that the CAG repeats did not affect male fertility. (Zhang et al., 2016)
PubMed
Amino Acid Substitution: Q43R
cDNA Position: 128 a→g (exon 2)
Disease Genetics Frequency Reference
Idiopathic sporadic Parkinson (Luoma et al., 2007)
PubMed
Reference # rs28567406
PubMed
Amino Acid Substitution: Q44X
cDNA Position: 132 del gc (exon 2)
Disease Genetics Frequency Reference
Reference # rs35424491
PubMed
Amino Acid Substitution: Q45R
cDNA Position: 134 a→g (exon 2)
Disease Genetics Frequency Reference
Epilepsy Found in trans w/ D136E <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Amino Acid Substitution: Q49E
cDNA Position: 145 c→g (exon 2)
Disease Genetics Frequency Reference
Neutral polymorphism <1 % in control populations (Luoma et al., 2007)
PubMed
Amino Acid Substitution: Q49X
cDNA Position: 147 del gc (exon 2)
Disease Genetics Frequency Reference
Reference # rs72434227
PubMed
Amino Acid Substitution: Q50X
cDNA Position: 149 del ag (exon 2)
Disease Genetics Frequency Reference
Reference # rs71879812
PubMed
Amino Acid Substitution: Q53X
cDNA Position: 158 del aa (exon 2)
Disease Genetics Frequency Reference
Reference # rs41550117
PubMed
Amino Acid Substitution: Q53-Q55dup
cDNA Position: 158 dup cag (exon 2)
Disease Genetics Frequency Reference
PEO Found in trans w/R964C in an 8 y.o. male with recessive ataxia, PEO, and hyoptonia Ohba et al., 2013
PubMed
Amino Acid Substitution: S64L
cDNA Position: 191 c→t (exon 2)
Disease Genetics Frequency Reference
Charcot-Marie-Tooth Found in cis with R232H in ar Charcot-Marie-Tooth 30.6% of control population (90/294 control alleles) (Harrower et al, 2008)
PubMed
Amino Acid Substitution: Q68X
cDNA Position: 202 c→t (exon 2)
Disease Genetics Frequency Reference
Alpers Found in trans w/ A467T (Wong et al., 2008)
PubMed
Amino Acid Substitution: L79F
cDNA Position: 235 c→t (exon 2)
Disease Genetics Frequency Reference
Epilepsy Found in compound with S1080I in an 8 yo female with adrenocortical insufficiency and hypothyroidy Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Epilepsy Found in compound with S1080I in an 8 yo female with epilepsy, cerebellar ataxia, and ptosis Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Amino Acid Substitution: L83P
cDNA Position: 248 t→c (exon 2)
Disease Genetics Frequency Reference
Alpers Compound heterozygous mutation with G888S in 10 yr. old (Bao et al., 2008)
PubMed
(Wong et al., 2008)
PubMed
Amino Acid Substitution: F88L
cDNA Position: 264 c→g (exon 2)
Disease Genetics Frequency Reference
Found in trans w/ A467T in a 42 y.o. w/ no symptoms noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: H110Y
cDNA Position: 328 c→t (exon 2)
Disease Genetics Frequency Reference
PEO Found as a heterozygous mutation in a and Complex I deficiency in a child from South India (Sonam et al., 2017)
PubMed
Heterozygous, hypotonia, failure to thrive, short stature, respiratory failure (Wong et al., 2008)
PubMed
Amino Acid Substitution: W113G
cDNA Position: 337 t→g (exon 2)
Disease Genetics Frequency Reference
Reference # rs77321104
PubMed
Amino Acid Substitution: P116Q
cDNA Position: 347 c→a (exon 2)
Disease Genetics Frequency Reference
Found in compound w/ T251I and P587L in an Italian 8 y.o. female with fatigue,hypotonia, and delayed psychomotor development with no mtDNA depletion. Diabetic father was positive for P116Q and the deaf mother was positive for T251I and P587L. 0 found in 200 chromosome controls (Scuderi, et al., 2015)
PubMed
Found in compound w/ T251I andP587L in an Italian 14 y.o. male with fatigue,hypotonia, left eye ptosis, migrains, but normal cognitive skills. Diabetic father was positive for P116Q and the deaf mother was positive for T251I and P587L. 0 found in 200 chromosome controls (Scuderi, et al., 2015)
PubMed
Amino Acid Substitution: D122Y
cDNA Position: 364 g→t (exon 2)
Disease Genetics Frequency Reference
Sensory axonal neuronopathy Found in a 67 y.o. female and her 61 y.o. brother. Found in compound w/Y837C, K601E, Q1236H. Both patients have an ataxia, dysarthria, seizures, and sensory neuropathies. Not found in 200 chromosome controls (Zabalza et al., 2014)
PubMed
Amino Acid Substitution: D136E
cDNA Position: 408 c→g (exon 2)
Disease Genetics Frequency Reference
Epilepsy Found in trans w/ Q45R <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Amino Acid Substitution: A143V
cDNA Position: 427 g→t (exon 2)
Disease Genetics Frequency Reference
Alpers Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA (Sarzi et al. 2007)
PubMed
PEO Found in trans w/ L304R in a 22 y.o. pt. with PEO and cerebral cavernous malformation. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ G848S in a 4 y.o. w/ hypotonia, encephalopathy, seizures, hepatic failure, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ G848S in a 38 y.o. w/ ataxia, peripheral neuropathy, hearing loss, and seizures Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A467T in an 8 y.o. w/ seizures and an abnormal MRI Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ G848S in a 37 y.o. symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in trans w/ A467T in a 49 y.o. w/ PEO, encephalopathy, ataxia, seizures, neuropathy, hearing loss, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in compound w/W748S and E1143G in a 40 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
Amino Acid Substitution: P163S
cDNA Position: 487 c→t (exon 2)
Disease Genetics Frequency Reference
Opthalmoplegia and seizures Found in trans w/T851A in a 21 y.o. female with peripheral neuropathy, seizures, dysarthria and bilateral ptosis 1 in 322 mitochondrial disease patients (Woodbridge et al., 2012)
PubMed
Amino Acid Substitution: E183X
cDNA Position: 547 del g (exon 2)
Disease Genetics Frequency Reference
Reference # rs35065786
PubMed
Amino Acid Substitution: R193Q
cDNA Position: 578 g→a (exon 2)
Disease Genetics Frequency Reference
Neutral polymorphism 0.6% of 450 individuals (GeneSNPs, 2004)
PubMed
Reference # rs3176162
PubMed
Amino Acid Substitution: A194V
cDNA Position: 580 g→t (exon 2)
Disease Genetics Frequency Reference
Inclusion body myositis Found as a heterozygous mutation in a Swedish patient with Inclusion body myostitis. In addition the patient had COX deficient muscle fibers, ragged red fibers, and mtDNA deletions. 1 in 26 patients with inclusion body myositis. 8 of which had heterozygous POLG mutations. (Lindgen et al., 2015)
PubMed
Amino Acid Substitution: C224Y
cDNA Position: 671 g→a (exon 3)
Disease Genetics Frequency Reference
Alpers Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA (Sarzi et al. 2007)
PubMed
Amino Acid Substitution: R227W
cDNA Position: 679 c→t (exon 3)
Disease Genetics Frequency Reference
PEO 36% of patients with sporadic PEO with multiple mtDNA deletions carry mutations in one of the three genes associated with familial arPEO or adPEO. Twinkle gene in 7% and POLG1 gene in 25% of our Italian and British patients with sporadic PEO. Found as compound in trans w/ S1176L.  Also, found as compound in trans with T251I-P587L. 7 out of 27patients w/sporadic PEO compared to 250 controls individuals. (Agostino et al., 2003)
PubMed
PEO Found as compound in trans w/ S1176L.  Also, found as compound in trans with T251I-P587L. (Lamantea and Zeviani, 2004)
PubMed
Alpers, Severe childhood multi-system disorder In Alpers found as compound with A467T. In severe childhood multi-system disorder found as compound with D1184N de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder (de Vries et al., 2007)
PubMed
Myopathy and gastrointestinal obstruction Found in trans w/ G848S with mtDNA depletion and Cox deficient muscle fibers (Giordano et al., 2009)
PubMed
Amino Acid Substitution: R227P
cDNA Position: 680 g→c (exon 3)
Disease Genetics Frequency Reference
Severe childhood multi-system disorder Compound heterozygous with A467T de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder (de Vries et al., 2007)
PubMed
Epilepsy and failure to thrive Found in trans w/ A467T <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Amino Acid Substitution: R232G
cDNA Position: 694 c→g (exon 3)
Disease Genetics Frequency Reference
Infantile Hepatocerebral Syndrome Found as compound with T251I and P587L Ferrari et al., 2005 reported 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with an allelic frequency of <0.14% (0 out of 350) in the control group. (Ferrari et al., 2005)
PubMed
Alpers Found in trans w/ [T251I and P587L] (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Hepatocerebral MDS Found in trans w/ [T251I andP587L] (Spinazzola et al., 2009)
PubMed
Amino Acid Substitution: R232H
cDNA Position: 695 g→a (exon 3)
Disease Genetics Frequency Reference
Liver failure, encephalopathy, and epilepsy Found as compound in trans with W748S - E1143G Not found in 200 control alleles (Kollberg et al., 2006)
PubMed
Charcot-Marie Tooth disease, (CMT) (profound cerebellar ataxia) Found in cis with the S64L SNP and in trans with G737R Not detected in 282 control alleles (Harrower et al, 2008)
PubMed
Amino Acid Substitution: R232H
cDNA Position: 697 g→a (exon 3)
Disease Genetics Frequency Reference
Leigh Syndrome In trans w/G848S (Taanman et al, 2008)
PubMed
Amino Acid Substitution: R232H
cDNA Position: 695 g→a (exon 3)
Disease Genetics Frequency Reference
Infantile hepatocerebral Found in trans w/A467T and in cis w/H277L in a 2 mo. mold w/hypotonia, motor paresis and developmentally delayed (Hunter et al., 2011)
PubMed
Amino Acid Substitution: R232H
cDNA Position: 697 g→a (exon 3)
Disease Genetics Frequency Reference
Infantile hepatocerebral Found in trans w/A467T and in cis w/H277L in a 1.5 mo. old w/hypotonia and developmentally delayed (Hunter et al., 2011)
PubMed
Infantile hepatocerebral Found W748S and E1143G w/ A467T in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Parkinsonism Found as a heterozygous mutation in a 25 yo male with sensorimotor neuropath, ataxia, and mtDNA deletions Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Sensorimotor neuropathy Found as a heterozygous mutation in a 30 yo female with axonal sensorimotor neuropathy Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Sensorimotor neuropathy Found as a heterozygous mutation in a 20 yo female with sensorimotor neuropath ,and ataxia Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
SANDO Found in trans w/T251I/P587L and in cis w/H277L in a 26 y.o. with PEO, cognitive impairment, ataxia, polyneuropathy, muscle weakness, migraines, dysphagia, and dysarthria. (Bereau et al., 2016)
PubMed
SANDO Found in trans w/T251I and P587L and in cis w/H277L in a 40 y.o. with PEO, ataxia, polyneuropathy, and dysarthria. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: W235X
cDNA Position: 705 g→a (exon 3)
Disease Genetics Frequency Reference
Severe childhood multi-system disorder Found as compound heterozygote with A467T de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder (de Vries et al., 2007)
PubMed
Amino Acid Substitution: Q238R
cDNA Position: 713 a→g (exon 3)
Disease Genetics Frequency Reference
Reference # rs56410699
PubMed
Amino Acid Substitution: P241L
cDNA Position: 722 c→t (exon 3)
Disease Genetics Frequency Reference
Neutral polymorphism <1 % in control populations (Luoma et al., 2007)
PubMed
Parkinsonism Found in a Chinese population with Parkinsonism at an allelic frequency of 0.326 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
Amino Acid Substitution: L244P
cDNA Position: 731 t→c (exon 3)
Disease Genetics Frequency Reference
Infantile Hepatocerebral Syndrome Found as compound with W748S 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with an allelic frequency of <0.14% (0 out of 350) in the control group. (Ferrari et al., 2005)
PubMed
Alpers Found 2 infants in trans with W748S (Spinazzola et al., 2009)
PubMed
Amino Acid Substitution: T251I
cDNA Position: 752 c→t (exon 3)
Disease Genetics Frequency Reference
PEO ar PEO. Found as compound with R309L, or 2354G insertion, or G848S in PEO.  1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls.  (Ferrari et al., 2005)
PubMed
PEO Found in compound with R807P (Del Bo et al., 2003)
PubMed
Infantile Hepatocerebral Syndrome Frequently found in cis with P587L and compound in trans with L304R, V1106I, and R227W . Not found in 250 control individuals (Horvath et al., 2006)
PubMed
PEO Found as compound in trans w/ S1176L, G848S, G785X, V1106I, R309L and R227W and cis w/ P587L.  Also, T251I/P587L was found as a homozygous mutation. (Lamantea and Zeviani, 2004)
PubMed
PEO and mtDNA deletions Found in compound w/P587L/ R807P in1 pt. and w/P587L/ H932Y in a 2nd pt. A 3rd pt. was found in compound w/P587L only. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions. 31 mitochondrial myopathy patients without any family history for the disorder (Di Fonzo et al., 2003)
PubMed
Infantile Hepatocerebral Syndrome 36% of patients with sporadic PEO with multiple mtDNA deletions carry mutations in one of the three genes associated with familial arPEO or adPE. Twinkle gene in 7% and POLG1 gene in 25% of our Italian and British patients with sporadic PEO. Found as compound in trans w/ R227W.  Also, found as compound in cis with P587L. 7 out of 27patients w/sporadic PEO compared to 250 controls individuals. (Agostino et al., 2003)
PubMed
MNGIE Found in cis with P587L and in trans w/N846S. Van Goethem, 2003: Not found in 280 control chromosomes ( Van Goethem et al., 2003c) 
PubMed
Infantile Hepatocerebral Syndrome Found in 1 of 9 infantile hepatocerebral syndrome patients. In cis with P587L and compound with R232G. 9 infantile hepatocerebral patients of German and Italian descent. (Ferrari et al., 2005)
PubMed
PEO POLG molecular defects were found in 25% of patients with multiple mtDNA deletions and mitochondrial disease. Found in trans w/M603L and in cis with P587L. 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez - Vioque et al., 2006) 
PubMed
PEO Found in trans w/ G848S and in cis w/ P587L in a 75 y.o. male. (Kollberg et al., 2005)
PubMed
Alpers Found in trans w/ G848S and in cis w/ P587L. Also found in cis w/P587L and in trans w/R853Q in myocerebralhepatopathy patient. Also found as a heterozygous mutation with ataxia, ptosis, and neuropathy. (Wong et al., 2008)
PubMed
Alpers Found in cis w/ R232G and cis w/ P587L. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
PEO Found in cis w/ P587L, with both mutations on each allele. A 2nd pt. found to have P587L in trans and A467T in cis. (Stewart et al., 2009)
PubMed
mtDNA depletion In cis w/P587L and in trans w/ E1136K (Taanman et al., 2008)
PubMed
Hepatocerebral MDS Found in cis with P587L and in trans with R232G (Spinazzola et al., 2009)
PubMed
Restless leg syndrome, ptosis, diplopia, limb weakness, blurred vision Found in trans with P587L. (Aitken, et al., 2009)
PubMed
PEO Found in trans with W748S andP587L (Tzoulis, et al., 2009)
PubMed
PEO and mental retardation Found in cis w/P587L and in trans w/ R275X <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
PEO, exercise intolerance, diabetes and a 2nd pt. w/ cataract and myopathy Found in cis w/P587L and in trans w/ A467T <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Ptosis Found in cis w/P587L and in trans w/ G848S <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Epilepsy and mental retardation ad, Found w/P587L <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Seizures, hypotonia, and developmental delay Found w/P587L (Burusnukul and de los Reyes, 2009)
PubMed
Acute disseminated encephalomyelitis Found w/P587L, found in one 4 y.o. patient with autoimmune central nervous system disease (Harris et al., 2010)
PubMed
SANDO Found sporadically w/P587L and G848S in a 80 y.o. male (Wiess and Saneto, 2010)
PubMed
Ptosis and myopathy Found in cis with P587L and in trans with P648R in a 59 y.o. male with dysphagia, dysphonia, myopathy, ptosis, and mtDNA deletions. Father had same symptoms. (Ferreira et al., 2011)
PubMed
PEO Found in cis w/ P587L and in trans w/ H932Y in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Peripheral Neuropathy Found in cis w/ P587L and in trans w/ H932Y in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in cis w/ P587L and in trans w/ G848S in an 80 y.o. w/ peripheral neuropathy, ptosis, and abnormal muscle histology Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in cis w/ P587L and in trans w/ K1191N in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in cis w/ P587L and in trans w/ N1157S in a 9 y.o. Symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ G588D and in cis w/ P587L in a 6 y.o. w/ no symptoms noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in compound with G848S in a 45 yo female with mtDNA deletions Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
SANDO Found in cis with P587L and in trans with A467T in a female in her 60's with a 5 year history of peripheral neuropathy, blurred vision, unstable gait, and sensory ataxia, dementia, and ophthalmoplegia. (Lovan et al., 2013)
PubMed
SANDO Found in cis w/P587L and in trans w/R869Q in a 34 y.o. female with ataxia, ptosis, diabetes and mtDNA deletions. (Hanisch et al., 2014)
PubMed
PEO Found in compound w/P587L and D1184N in a 33 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
PEO Found in compound w/P587L and D1184N in a 30 y.o. male patient w/ chronic intestinal pseudo-obstruction and PEO. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
Found in compound w/ P116Q and P587L in an Italian 8 y.o. female with fatigue,hypotonia, and delayed psychomotor development with no mtDNA depletion. Diabetic father was positive for P116Q and the deaf mother was positive for T251I and P587L. 0 found in 200 chromosome controls (Scuderi, et al., 2015)
PubMed
Found in compound w/ P116QI andP587L in an Italian 14 y.o. male with fatigue,hypotonia, left eye ptosis, migrains, but normal cognitive skills. Diabetic father was positive for P116Q and the deaf mother was positive for T251I and P587L. 0 found in 200 chromosome controls (Scuderi, et al., 2015)
PubMed
Parkinsonism and PEO Found in cis w/P587L and in trans w/W468X. Found in a 68 y.o. female w/ exercise intolerance, PEO, facial diparesis, and left-dominant postural tremor. (Miguel, et al., 2014)
PubMed
PEO Found in cis with P587L and in trans w/W748S in a 50 y.o.with PEO and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/G848S and in cis w/P587L with PEO, muscle weakness, and cognitive impairment. Similar to SANDO, but no dysarthria. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/S1095R and in cis w/P587L with PEO, muscle weakness, ataxia, and polyneuropathy. Similar to SANDO, but no dysarthria. (Bereau et al., 2016)
PubMed
SANDO Found in cis w/P587L and in trans w/R232H and H277L in a 26 y.o. with PEO, cognitive impairment, ataxia, polyneuropathy, msucle weakness, migraines, dysphagia, and dysarthria. (Bereau et al., 2016)
PubMed
PEO Found in cis with P587L and in trans w/A467T in a 30 y.o. with muscle weaknes and PEO. (Bereau et al., 2016)
PubMed
SANDO Found in cis w/P587L and in trans w/R232H and H277L in a 40 y.o. with PEO, ataxia, polyneuropathy, and dysarthria. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/R852C and in cis w/P587L in a 50 y.o. with PEO, muscle weakness, and polyneuropathy. Similar to SANDO, but no dysarthria. (Bereau et al., 2016)
PubMed
PEO Found in trans w/A467T and in cis w/P587L in a 56 y.o. with PEO, muscle weakness, and dysphagia. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/A467T and in cis w/P587L in a 58 y.o. with ataxia, sensory neuropathy, and dysphagia. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/A467T and in cis w/P587L in a 66 y.o. with ataxia, sensory neuropathy, and PEO. (Bereau et al., 2016)
PubMed
PEO Found in cis w/P587L on both allesls with ptosis and dysphagia (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/T251I and P587L with ataxia, sensory neruopathy, PEO, deafness, and dysphagia. (Bereau et al., 2016)
PubMed
PEO Found in cis with P587L and in trans w/T989dup in a 36 y.o. female with cornieal edema and muscle weakness. One brother affected and has both variants and one unaffected sister with no mutations. Not found in 100 random controls (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: G268A
cDNA Position: 803 g→c (exon 3)
Disease Genetics Frequency Reference
PEO Sporadic / unknown Found as compound in trans with A467T Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians  (Di Fonzo et al., 2003)
PubMed
PEO Sporadic / unknown Found as compound in trans with A467T (Del Bo et al., 2003)
PubMed
PEO Sporadic / unknown Found as compound in trans with A467T (Baruffini et al., 2006)
PubMed
PEO Sporadic / unknown Found as compound in trans with A467T 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez - Vioque et al., 2006)
PubMed
Parkinsonism, dystonia, mental retardation, hepatocerebral syndrome, ptosis, neuropathy, and intestinal problems ar, 3 patients ages 3-16 yrs <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Reference # rs61752784
PubMed
Amino Acid Substitution: R275X
cDNA Position: 823 c→t (exon 3)
Disease Genetics Frequency Reference
PEO and mental retardation Found in trans w/ T251I+P587L <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Amino Acid Substitution: R275Q
cDNA Position: 824 g→a (exon 3)
Disease Genetics Frequency Reference
Multiple Sclerosis-like illness and PEO Found as a heterozygous mutation w/A467T in a 63 y.o. Pt. first diagnosed w/ optic neuritis and MS 33 yrs earlier. Currently, pt. has ragged-red muscle fibers, ptosis, myopathies, PEO, and mtDNA deletions. (Echaniz-Laguna et al., 2010)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/A467T in a 62 y.o. with ataxia, sensory neuropathy and PEO. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: H277L
cDNA Position: 830 a→t (exon 3)
Disease Genetics Frequency Reference
Alpers Found in trans w/T851A (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Infantile hepatocerebral Found in trans w/A467T and in cis w/R232H in a 2 mo. old w/hypotonia, motor paresis and developmentally delayed (Hunter et al., 2011)
PubMed
Infantile hepatocerebral Found in trans w/A467T and in cis w/R232H in a 1.5 mo. old w/hypotonia and developmentally delayed (Hunter et al., 2011)
PubMed
Myelopathy,myopathy, peripheral neuropathy and subcortical grey matter degeneration Found in trans w/A862T in a 66 y.o. female with mtDNA deletions and subcortical grey matter degeneration (McKelvie et al., 2012)
PubMed
Parkinsonism Found in trans w/R943C in a 78 y.o. Japanese male with parkinsonism. Not found in 50 ethnically matched controls (Sato et al., 2011)
PubMed
SANDO Found in trans w/R232H and in cis w/T251I andP587L in a 26 y.o. with PEO, cognitive impairment, ataxia, polyneuropathy, msucle weakness, migraines, dysphagia, and dysarthria. (Bereau et al., 2016)
PubMed
SANDO Found in trans w/T251I and P587L and in cis w/R232H in a 40 y.o. with PEO, ataxia, polyneuropathy, and dysarthria. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: Y282D
cDNA Position: 844 t→g (exon 3)
Disease Genetics Frequency Reference
Alpers Found in trans w/L304R in a patient with intractable convulsions and severe epileptic status. 1 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome (Navarro-Sastre et al., 2012)
PubMed
Amino Acid Substitution: R290C
cDNA Position: 868 c→t (exon 4)
Disease Genetics Frequency Reference
Epilepsy and devleopmental delay Found in a 5 month old male with infantile spasms and global developmental delays (Wang et al., 2017)
PubMed
Amino Acid Substitution: G303R
cDNA Position: 907 a→g (exon 4)
Disease Genetics Frequency Reference
Encephalopathy Found in trans w/ A467T in 2 brothers and a 3rd unrelated pt. All 3 had ataxia, epilepsy, and encephalopathy. Not found in 170 control individuals (Tzoulis, et al., 2010)
PubMed
Alpers Found in trans w/ A467T in a pediatric patient w/mitochondrial encelphalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Encephalopathy Found w/A467T in a 9 mo. child w/epilepsy and death at 1.1 yrs. (Tzoulis et al., 2014)
PubMed
Encephalopathy Found w/A467T in a 2 y.o child w/epilepsy, ataxia, and death at 8.0 yrs. (Tzoulis et al., 2014)
PubMed
Amino Acid Substitution: L304R
cDNA Position: 911 t→g (exon 4)
Disease Genetics Frequency Reference
PEO Ataxia - neuropathy ar  Compound in trans with A467T  Found as homozygous or compound in trans with W748S - E1143G in SCAE, ataxi-neuropathy Van Goethem et al., 2001 reported 0 out of 229 control Individuals (<0.4%) (Van Goethem et al., 2001)
PubMed
PEO Ataxia - neuropathy ar  Compound in trans with A467T  Found as homozygous or compound in trans with W748S - E1143G in SCAE, ataxi-neuropathy Not found in 300 healthy French control chromosomes (Naimi et al., 2006)
PubMed
PEO Ataxia - neuropathy ar  Compound in trans with A467T  Found as homozygous or compound in trans with W748S - E1143G in SCAE, ataxic-neuropathy ( Stuart et al., 2006)
PubMed
Alpers Found homozygous in one pt. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Alpers Found in trans w/ L392V and R1081dup. (Cardenas et al., 2010)
PubMed
VPA induced liver toxicity Found in trans with A467T in a 15 y.o. pt. with VPA induced hepatotoxicity Used 968 alleles ethnically matched controls (Stewart et al., 2010)
PubMed
Peripheral neuropathy Found as a homozygote in a 23 y.o. pt. with exercise intolerance, muscle weakness, and ragged red fibers. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ D1145GfsX9 in a developmentally delayed 12 y.o. with seizures and hypotonia. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in trans w/ G737R in a 54 y.o. w/PEO, ptosis, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found as a homozygote in a 12 y.o. w/ PEO, ptosis, neuropathy, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found as a homozygote in a 9 y.o. with PEO, neuropathy, ptosis, and COX deficient fibers. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found as a homozygote in a 2 y.o. pt. w/ encephalopathy, seizures, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in trans w/ A143V in a 22 y.o. pt. with PEO and cerebral cavernous malformation. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found as a homozygote in a 9 y.o. with ptosis, ataxia, hypotonia, and cerebellar atrophy. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found has a homozygote in a 4 y.o. w/ seizures, ptosis, and an abnormal MRI. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found as a homozygote in a 10 y.o. w/ ptosis, PEO, ataxia, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ A467T in a 15 y.o. symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ R1081dup in a 1 y.o. w/seizures and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in trans w/ R1081P in a 10 y.o. w/ ataxia, seizures, PEO, and dystonia Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Alpers Found in trans w/G888D in a patient showing psychomotor retardation, epileptic encephalopathy, progressive cerebral atrophy, and altered liver enzymes. 2 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome (Navarro-Sastre et al., 2012)
PubMed
Alpers Found in trans w/Y282D in a patient with intractable convulsions and severe epileptic status. 2 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome (Navarro-Sastre et al., 2012)
PubMed
SANDO Found as a homozygous mutation in a 15 yo male with 40% COX neg muscle fibers and multiple mtDNA deletions Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
PEO Found in compound with W748S in a 27 yo female with sensory and cerebellar ataxia, axonal sensory neuropathy Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
PEO Found in trans w/c.1713-21 in a 23 y.o.with PEO, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
SCAE Found in trans w/W748S with PEO, cognitive impairment, seizures, ataxia, polyneuropathy, dysphagia, and dysarthria. (Bereau et al., 2016)
PubMed
SANDOS Found as a homozygous mutation w/ multiple complex deficiencies in a child from South India (Sonam et al., 2017)
PubMed
Ataxia neuropathy Found as a homozygous mutation w/ multiple complex deficiencies in a child from South India (Sonam et al., 2017)
PubMed
Amino Acid Substitution: S305R
cDNA Position: 915 c→g (exon 4)
Disease Genetics Frequency Reference
Alpers heterozygous (Wong et al., 2008)
PubMed
Alpers Found in trans w/A467T <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Alpers Found as a compound heterozygote w/P1073L. (Baruffini et al., 2011)
PubMed
Epilepsy and ataxia-neuropathy Heterozygous mutation w/R627Q found in a 5 y.o. pt. w/epilepsy at age 5, and developed ataxia and neuropathy in his teens. (Baruffini et al., 2011)
PubMed
Liver Failure Found in trans w/ A467T in a 1 y.o. with liver failure Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Alpers Found in trans w/A467T in a 3 y.o. w/seizures and developmentally delayed (Hunter et al., 2011)
PubMed
Amino Acid Substitution: Q308H
cDNA Position: 924 g→c (exon 4)
Disease Genetics Frequency Reference
PEO Found in trans w/W748S Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Amino Acid Substitution: R309L
cDNA Position: 926 g→t (exon 4)
Disease Genetics Frequency Reference
PEO ar, Compound with T251I Not found in 100 DNA samples (Lamantea et al., 2002)
PubMed
Amino Acid Substitution: R309H
cDNA Position: 926 g→a (exon 4)
Disease Genetics Frequency Reference
Alpers Compound in trans with R627Q Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Epilepsy ataxia and developmental delay Found in trans with G1051R in a 32 y.o. male with severe neuropathy, achalasia, epilepsy, and developmentally delayed. (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: R309C
cDNA Position: 925 c→t (exon 4)
Disease Genetics Frequency Reference
PEO Found in a heterozygous 14 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, ataxia, myopathy, and COX negative fibers In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
MELAS Found in trans w/ W748C in an 18 y.o. female with seizues, vision loss, neuropathy, ophthalmoparesis. Each parent is an unaffected heterozygote. (Ching-wan et al., 2015)
PubMed
Amino Acid Substitution: W312R
cDNA Position: 934 t→c (exon 4)
Disease Genetics Frequency Reference
PEO Found in a 39 y.o. with PEO as a heterozygous mutation 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG (Agostino et al., 2003)
PubMed
Encephalopathy, dysphagia, and neuropathy Found in trans with R574W in a 62 y.o. male Not found in 250 control individuals (Horvath et al., 2006)
PubMed
PEO Found as a homozygous mutation in a 58 y.o. male with dysphagia, dysphonia cataract, and mild myopathy. (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: K319E
cDNA Position: 955 a→g (exon 4)
Disease Genetics Frequency Reference
PEO Found in trans w/ R869Q in a 44 y.o. w/ PEO, ataxia, neuropathy, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: P324S
cDNA Position: 970 t→g (exon 4)
Disease Genetics Frequency Reference
Neutral polymorphism 0.6% of 450 individuals (GeneSNPs, 2004)
PubMed
Reference # rs2307437
PubMed
Amino Acid Substitution: T326fs61X
cDNA Position: 975-976 ins c stop@387 (exon 4)
Disease Genetics Frequency Reference
Alpers Found in trans with A467T Not found in 300 healthy French control chromosomes (Naimi et al., 2006)
PubMed
Alpers Found in compound with A467T in a 4 yo male with mtDNA depletion Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Amino Acid Substitution: S332X
cDNA Position: 994 del c or tc→g (exon 4)
Disease Genetics Frequency Reference
Reference # rs35954915
PubMed
Amino Acid Substitution: W347_L356 del
cDNA Position: 1039-1068 del (exon 5)
Disease Genetics Frequency Reference
Alpers 10 amino acid del found in trans w/A467T (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Amino Acid Substitution: E358A
cDNA Position: 1073 a→c del364X (exon 4)
Disease Genetics Frequency Reference
Alpers Found in trans w/A467T in a 3 y.o. w/seizures, ataxia, and developmentally delayed (Hunter et al., 2011)
PubMed
Amino Acid Substitution: E358A
cDNA Position: 1073 a→c del364X (exon 4)
Disease Genetics Frequency Reference
Alpers Found in trans w/A467T in a 4 y.o. w/seizures, ataxia, and developmentally delayed (Hunter et al., 2011)
PubMed
Amino Acid Substitution: R374X
cDNA Position: 1120 c→t (STOP) (exon 5)
Disease Genetics Frequency Reference
Alpers Found in trans w/A467T. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Amino Acid Substitution: G380D
cDNA Position: 1139 g→a (exon 5)
Disease Genetics Frequency Reference
PEO Sporadic mutation found in trans with A467T Not found in 300 healthy French control chromosomes (Naimi et al., 2006)
PubMed
PEO Found in compound with A467T in a 63 yo male with cerebellar ataxia, weakness of lower limbs and cognitive impairment Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Amino Acid Substitution: R386C
cDNA Position: 1156 c→t (exon 5)
Disease Genetics Frequency Reference
Isolated distal myopathy of upper limbs and mtDNA depletion Found as a compound heterozygote w/ H932Y in one 27 y.o. male. Recessive inheritance of both mutated alleles confirmed. (Giordano et al., 2010)
PubMed
Amino Acid Substitution: R386H
cDNA Position: 1157 g→a (exon 5)
Disease Genetics Frequency Reference
Alpers Heterozygous single mutation found in a 1 y.o.. (Baruffini et al., 2011)
PubMed
Amino Acid Substitution: L392V
cDNA Position: 1174 c→g (exon 6)
Disease Genetics Frequency Reference
Neutral polymorphism Heterozygous with muscle weakness & optic atrophy <1 % in control populations (Luoma et al., 2007) (Wong et al., 2008)
PubMed
Alpers Found in cis w/R1081dup and in trans w/L304R (Cardenas et al., 2010)
PubMed
Amino Acid Substitution: L392W
cDNA Position: 1174 ct→tg (exon 6)
Disease Genetics Frequency Reference
Found in a Chinese population with Parkinsonism at an allelic frequency of 0.199 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
Amino Acid Substitution: L411P
cDNA Position: 1232y→c (exon 6)
Disease Genetics Frequency Reference
Progressive ataxia and epilepsy Found in trans w/ R574W in a 69 y.o. female with progressive gait ataxia, dysarthria, and myoclonic jerks. ( Ng et al., 2017)
PubMed
Amino Acid Substitution: P412L
cDNA Position: 1235 c→t (exon 6)
Disease Genetics Frequency Reference
Ataxia Found as a heterozygous mutation in a 64 y.o. female with mtDNA deletions, spastic ataxic gait, and multiple lipomas. (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: R417T
cDNA Position: 1250 g→c (exon 6&7 junction)
Disease Genetics Frequency Reference
Alpers Found in trans w/A467T (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Amino Acid Substitution: Exon 7 deletion
cDNA Position: c.1251-2 a→t (exon 6&7 splice site)
Disease Genetics Frequency Reference
Alpers Found as a compound heterozygote with A467T. The pt. was a 3.5 y.o. male with VPA induced liver toxicity. (Schaller et al., 2011)
PubMed
Amino Acid Substitution: C418R
cDNA Position: 1252 t→c (exon 7)
Disease Genetics Frequency Reference
Alpers Found in trans w/A467T. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Alpers Found in trans w/A467T in a 43 mo. old female with ataxia and seizures (McCoy et al., 2011)
PubMed
Amino Acid Substitution: L424GfsX28
cDNA Position: 1270-1271 del ct stop @ 452 (exon 7)
Disease Genetics Frequency Reference
PEO Sporadic / unknown Compound with G431V 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG (Agostino et al., 2003)
PubMed
Alpers Found in trans with A467T (Wong et al., 2008)
PubMed
Amino Acid Substitution: G426S
cDNA Position: 1276 g→a (exon 7)
Disease Genetics Frequency Reference
Epilepsy, ataxia, myoclonus, cataract, and cognitive delay ar, found in a 56 yr. old pt. with 2 siblings with epilepsy <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Seizures Found in trans w/ G737R in an 11 y.o. w/ seizures and an abnormal MRI Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: L428P
cDNA Position: 1283 t→c (exon 7)
Disease Genetics Frequency Reference
Alpers Found as a heterozygote w/ A467T. Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation L428P. 19% (9 out of 50) had various mutations in POLG. (Sarzi et al. 2007)
PubMed
Amino Acid Substitution: M430L
cDNA Position: 1288 a→t (exon 7)
Disease Genetics Frequency Reference
PEO with Parkinsonism ar, Compound (in trans) heterozygous with W918R Absent in 200 control alleles (Invernizzi et al., 2008)
PubMed
PEO Found in trans with W918R in a 42 y.o. male with PEO and mtDNA deletions (Ferreira et al., 2011)
PubMed
Amino Acid Substitution: G431V
cDNA Position: 1292 g→t (exon 7)
Disease Genetics Frequency Reference
PEO Sporadic / unknown Compound with L424 CT deletion 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG (Agostino et al., 2003)
PubMed
Amino Acid Substitution: S433C
cDNA Position: 1298 c→g (exon 7)
Disease Genetics Frequency Reference
PEO- ataxia, peripheral neuropathy Found in trans with E1143G in a patient with PEO, ataxia, peripheral neuropathy, and episodes of encephalopathy. Mother had heterozygous E1143G variant, but was asymptomatic. Hudson, 2006: Not detected in 200 controls (Hudson et al., 2006a)
PubMed
PEO Sporadic, Found in trans with E1143G Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Amino Acid Substitution: Q449X
cDNA Position: 1345 c→t (exon 7)
Disease Genetics Frequency Reference
Alpers Found in trans w/ W748S in a 21 y.o. with seizures Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: Y452X
cDNA Position: 1356 t→g (exon 7)
Disease Genetics Frequency Reference
PEO Sporadic Not detected in 200 controls. (Hudson et al., 2006a)
PubMed
Multiple Sclerosis-like illness Found as a heterozygous mutation w/T914A in a 56 yr. old. Pt. first diagnosed w/ optic neuritis and MS 19 yrs earlier. Currently has ragged-red muscle fibers, ptosis, myopathies, and mtDNA deletions. (Echaniz-Laguna et al., 2010)
PubMed
Amino Acid Substitution: L463F
cDNA Position: 1389 g→t (exon 7)
Disease Genetics Frequency Reference
PEO ar, Found as compound in trans with S511N None found in 192 ethnically matched control chromosomes nor in 108 patients with PEO and 140 cases of sporadic PD (Hudson et al., 2006b)
PubMed
Amino Acid Substitution: M464T
cDNA Position: 1391 t→c (exon 7)
Disease Genetics Frequency Reference
neuropathy and ataxia Found in compound with K768E in a teenage female with axonal sensorimotor neuropathy and sensory ataxia with multiple mtDNA deletions Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Amino Acid Substitution: A467T
cDNA Position: 1399 g→a (exon 7)
Disease Genetics Frequency Reference
PEO Found as compound with L304R and R3P in PEO.  Also found as a homozygous mutation in a PEO pt. Three out of 229 control individuals were heterozygous for A467T (allele T frequency 0.6%), while the R3P and L304R mutations were not observed. (Van Goethem et al., 2001)
PubMed
PEO Found as compound with S1104C in a 48 y.o. pt. with PEO  7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG (Agostino et al., 2003)
PubMed
PEO Found in compound with G268A Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians  (Di Fonzo et al., 2003)
PubMed
PEO Found as compound with R627Q, L304R or R3P, or G268A   Van Goethem, 2003: absent in 612 Belgian controls. (Van Goethem et al., 2003a)
PubMed
MERRF homozygous mutation in an 18 y.o. patient w/ myoclonus, seizure, and sensory ataxic neuropathy (Van Goethem et al., 2003b)
PubMed
Alpers Found in compound het with E873stop in Alpers w/ mtDNA depletion (Naviaux and Nguyen, 2004)
PubMed
Neurodegenerative disorders and ataxia Found as a homozygous mutation in 2 of 8 patient w/ ataxia and neurological disorders. Also found in trans with E1143G/W748S in a 2nd patient. (Van Goethem et al., 2004)
PubMed
(Chan et al., 2005a)
PubMed
Alpers Studied Alpers pt. fibroblasts with the compound het with E873stop w/ mtDNA depletion. Determined that transcripts containing this stop codon undergo nonsense-associated alternative splicing and nonsense-mediated decay. (Chan et al., 2005b)
PubMed
Infantile Hepatocerebral Syndrome Found as a homozygous mutation in 1 of 9 pts. with progressive neurological and hepatic failure.  Also found as in trans w/G848S and a 3rd pt. in trans w/ A957P. Also found in trans with 3482 +2t's splice site variant in a 4th pt. 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with an allelic frequency of <0.14% (0 out of 350) in the control group. ( Ferrari et al., 2005)
PubMed
ataxia-myopathy syndrome Found as a heterozygous mutation in 4 family members, and found in compound with R627Q in a 5th family member. ( Luoma et al., 2005)
PubMed
Alpers Found in trans w/ W1020X in two infants and also in trans w/ G848S in two other infants. Found as a homozygous mutation in an 8.5 y.o. male. (Nguyen et al., 2005)
PubMed
Ataxia Syndrome Found as a homozygous mutation in 2 members of the same family with mtDNA deletions (Winterthun et al., 2005)
PubMed
PEO Found as a homozygous mutation in a 33 y.o. male with mtDNA deletions 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez-Vioque et al., 2006)
PubMed
Encephalopathy, liver disorders, and PEO A467T is common in children, but complete POLG1 sequencing is required to identify multiple mutations that can have complex implications for genetic counseling. Studied a large collection of patients with clinical, biochemical and molecular genetic evidence of mitochondrial disease from several European research clinics. Found as compound in trans with K1191N, G848S, T914P, c. 2480+1g>a, E1143G + Q879H, 3482+2t>c, W748S, E1143G, and R627W.. Found as homozygous mutation in4 patients. Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Oxidative phosphorylation enzyme complex deficiencies Found as a homozygous mutation in 1 of 8 patients. Also found in trans w/ R227W, R227P, W235X, G848S, and A957P. de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder (de Vries et al., 2007)
PubMed
Liver failure, encephalopathy, and epilepsy Found in trans w/ R574W, G848S, W748S in children w/ progressive encephalopathy. Not found in 200 control alleles (Kollberg et al., 2006)
PubMed
Alpers Found in trans w/ T914P, T326fsX38, and G380D Not found in 300 healthy French control chromosomes (Naimi et al., 2006)
PubMed
Epilepsy, PEO, and ataxia Found as a homozygous mutation in 5 mitochondrial disease pts. Also, found in trans w/W748S in 6 pts. with mitochondrial disease. Studied in 26 mitochondrial disease patients (Tzoulis et al., 2006)
PubMed
PEO Identified a diverse range of phenotypes arising from PEO-associated amino acid substitutions introduced in the yeast pol gamma gene. (Stuart et al., 2006)
PubMed
Alpers Found as a heterozygote mutation with L428P. Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation L428P. 19% (9 out of 50) had various mutations in POLG. (Sarzi et al., 2007)
PubMed
Alpers w/ valporate induced hepatic failure Found in cis w/T885s and in trans w/Q879H and E1143G. (McFarland et al., 2008)
PubMed
Alpers, Ataxia Neuropathy, and arPEO+ Found in trans w/ L886P, Q68X, Q715X, T849H, T914P, L83P, G888S, R1138C, c.2480+1, c. 2157+5, G737R, and L424G (Wong et al., 2008)
PubMed
Alpers Found in trans w/ [R852C and G11D], and, found in trans w/ T914P in 2 additional pts.  In trans w/E873X.  In trans w/ W347_L356 del.  In trans w/G848S.  In trans w/L966R.  In trans w/R374X.  In trans w/ R417T.  In trans w/C418R.  One pt., found as a homozygous mutation. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Alpers, PEO Found in trans w/L605R, and in a 2nd pt. in trans w/ W748S. Also, found as a homozygous mutation.  Found in trans w/ T251I and P587L. Also found in trans w/ G11D and R852C. Also found in trans w/G848S. (Stewart et al., 2009)
PubMed
Alpers Found in trans w/T914P (Taanman et al., 2008)
PubMed
Alpers Found in trans w/ R574W (Spinazzola et al., 2009)
PubMed
Alpers Homozygous (Spinazzola et al., 2009)
PubMed
Alpers Found in trans w/ splice variant c.3643 +2t>c (Roels, et al., 2009)
PubMed
mtDNA depletion Found in trans w/ G8484S. (Roels, et al., 2009)
PubMed
Prematurity, epilepsy, deafness, retinitis pigmentosa, hemiparesis, and liver failure Found in trans w/ K925RfsX42 <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Alpers 5 patients found with a homozygous mutation <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Epilepsy and failure to thrive Found in trans w/ R227P <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
PEO, exercise intolerance, diabetes, and a 2nd pt. w/ cataract and myopathy 2 patients; found in trans w/ T251I + P587L <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Alpers Found in trans w/S305R <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
PEO, ptosis, polyneuropathy, ataxia, and dysarthria Found in trans w/ W748S and in compound w/ E1143G <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Epilepsy, myoclonus, polyneuropathy, ataxia, and cognitive delay; a 2nd pt. with epilepsy and MELAS-like symptoms Found in trans w/ W748S <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Epilepsy, myoclonus, and developmental delay Found in trans w/T914P <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Epilepsy, liver failure, occipital strokes, and growth retardation Found in trans w/ A957P <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Spinocerebellar ataxia, neuro-degeneration, and impaired cognitive functions ar, 2 patients ages 19 and 48 <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Epilepsy and myoclonus ar, found with E1143G <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Found with W748S in a 43 yr. old patient (Schulte et al., 2009)
PubMed
Cerebellar ataxia, sensory neuropathy, and dysphagia Homozygous. Found in 2 early 20 yr. old sisters, and only one with epilepsy (Schulte et al., 2009)
PubMed
SANDO Homozygous. Found in 2 siblings in their mid 40's. mtDNA deletions and COX1 deficient fibers in muscle biopsies (McHugh et al., 2010)
PubMed
Alpers Found in trans with G848S (Hasselmann et al., 2009)
PubMed
Hepatocerebral - Alpers symptoms Found in trans w/P1073L in 2 pt., Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility. (Kurt et al., 2010)
PubMed
Encephalopathy Found in trans w/ G303R in 2 brothers and a 3rd unrelated pt. All 3 had ataxia, epilepsy, and encephalopathy. Not found in 170 control individuals (Tzoulis et al., 2010)
PubMed
SANDO Found in trans with W748S+E1143G. Sensory ataxia, dysarthria, and opthalmoplegia. (Posada et al., 2010)
PubMed
Alpers Found as a compound heterozygote w/ a 4.7 kb POLG deletion from intron 14 thru intron 21 w/ a CGH array. Patient had early on set of Alpers and died at the age of 3.5 y.o.. The father carried the A467T mutation, and the mother the deletion. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Compton et al., 2010 and Tang et al., 2011)
PubMed
Multiple Sclerosis-like illness Found as a heterozygous mutation w/R275Q in a 63 yr. old. Pt. first diagnosed w/ optic neuritis and MS 33 yrs earlier. Currently, pt. has ragged-red muscle fibers, ptosis, myopathies, PEO, and mtDNA deletions. (Echaniz-Laguna et al., 2010)
PubMed
Alpers Found in trans w/ P625R in a 1 y.o. with epilepsy and liver failure. (Baruffini et al., 2011)
PubMed
Epilepsy Found heterozygous with T 914P in a 10 mo. old male with myoclonic seizures and jerks, and developmental regression. (Dhamija et al., 2011)
PubMed
Alpers Found in trans with E1143G, Q497H and W748S in a 6 y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Alpers Found in trans with T914P in a 9 mo. old with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
VPA induced liver toxicity Found in trans with L304R in a 15 y.o. pt. with VPA induced hepatotoxicity Used 968 alleles ethnically matched controls (Stewart et al., 2010)
PubMed
Alpers Found as a compound heterozygote with the splice site mutation c.1251-2a→t resulting in the deletion of exon 7. The pt. was a 3.5 y.o. male with VPA induced liver toxicity (Schaller et al., 2011)
PubMed
Encephalopathy Found in trans with Q715X in a 5 y.o. pt. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Liver Diseases Compound heterozygote in cis with W748S Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ T914P in a 3 y.o. with hypotonia, encephalopathy, seizures, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ G848S in an 8 y.o. pt. with seizures, muscle weakness, hypotonia, ataxia, hearing loss, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ G848S in a 1 y.o. pt. with seizures and elevated transaminases, and increased signal basal ganglia Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
SANDO AND PEO Found in trans w/ W748S in a 54 y.o. with PEO, ptosis, ataxia, neuropathy, and SANDO Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ W748S in a 16 y.o. with seizures, dystonia, choria, neuropathy, and ptosis Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Encephalopathy and ataxia Found in trans w/ R597W in a 26 y.o. with encephalopathy, ataxis, ptosis, and neuropathy Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/K1050RfsX44 in a 4 y.o. w/ seizures, ataxia, hypotonia, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found as a homozygote in a 46 y.o. pt. w/ ptosis, neuropathy, muscle weakness, and ataxia Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/W748S in an 18 y.o. with ataxia, seizures, dystonia, and optic atrophy. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Ataxia Found as a homozygote in a 48 y.o. w/ hypotonia, ataxia muscle weakness, and headaches. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A467T in a 2 y.o. w/ hypotonia, encephalopathy, seizures, cardiomyopathy, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found as a homozygote in a 19 y.o. w/ ataxia, myoclonic seizures, optic atrophy, dysarthria, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO and seizures Found as a homozygote in a 40 y.o. w/ PEO, ataxia, seizures, and neuropathy Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ L1113P in a 1 y.o. with encephalopathy, seizures, and hepatic failure Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ T914P in a 5 y.o. w/ seizures, hearing loss, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Liver failure Found in trans w/ S305R in a 1 y.o. with liver failure Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures and liver failure Found in trans w/ R852C and G11D in a 8 mo. w/ seizures, liver failure, and lactic acidosis. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ F749S in a 6 y.o. w/ seizures Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Hepatic failure Found in trans w/ S1095R in a 6 mo. w/ hypotonia, liver failure, abnormal muscle histology, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ T914P in a 9 mo. w/ seizures, hypotonia, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures and hepatic failure Found in trans w/ T914P in a 4 y.o. with liver failure, seizures, and failure to thrive Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ Q1024X in a 2y.o. w/seizures, hearing loss, and hemiparesis Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ W748S in a 29 y.o. symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in trans w/ A143V in a 49 y.o. w/ PEO, encephalopathy, ataxia, seizures, neuropathy, hearing loss, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ L304R in a 15 y.o. Symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Liver failure Found in trans w/ R807C in a 1 y.o. w/ encephalopathy, liver failure, and lactic acidosis Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ T914P in an 8 mo. w/ seizures, respiratory failure, and an abnormal MRI Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ F749S in an 8 mo. symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures and hepatic failure Found in trans w/ H754Q in a 2 y.o. w/ seizures, hepatic failure, and cerebellar atrophy. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ C1188R in a 3 y.o. w/ seizures, hypotonia, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
VPA induced liver failure Found in trans w/ G588D in a 2 y.o. w/ VPA induced liver failure Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ F88L in a 42 y.o. w/ no symptoms noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Alpers Found in trans w/G848S in a 3 y.o. w/seizures, developmentally delayed, and ataxia (Hunter et al., 2011)
PubMed
Alpers Found in trans w/G848S in a 11 mo. old w/seizures and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found as a homozygous mutation in a 10 y.o. w/seizures and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/IVS14+1G>A in a 2 y.o. w/seizures, developmentally delayed, and ataxia (Hunter et al., 2011)
PubMed
Alpers Found in trans w/R852C in a 5 y.o. w/seizures, ataxia, and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/S305R in a 3 y.o. w/seizures and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/L966R in a 1 y.o. w/ seizures and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/E358A del364X in a 3 y.o. w/seizures, ataxia, and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/E358A del364X in a 4 y.o. w/seizures, ataxia, and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/L966R in a 1 y.o. w/ seizures and developmentally delayed (Hunter et al., 2011)
PubMed
Infantile hepatocerebral Found in trans w/R232H and H277L in a 2 mo. old w/hypotonia, motor paresis and developmentally delayed (Hunter et al., 2011)
PubMed
Infantile hepatocerebral Found in trans w/R232H and H277L in a 1.5 mo. old w/hypotonia and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/ R574W in 2 pediatric patients w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Alpers Found in trans w/ G848S in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Alpers Found in trans w/ G303R in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Alpers Found in trans w/L966R in a 17 mo. old male with seizures and encephalopathy (McCoy et al., 2011)
PubMed
Alpers Found in trans w/G848S in a 10 mo. old female with seizures and brain stem dysfunction. History revealed that a 24 y.o. cousin died from Alpers whom harbored a homozygous A467T variant. (McCoy et al., 2011)
PubMed
Alpers Found in trans w/R852C in a 21 mo. old female with blindness, anarthria, hypotonia, and epilepsy (McCoy et al., 2011)
PubMed
Alpers Found in trans w/C418R in a 43 mo. old female with ataxia and seizures (McCoy et al., 2011)
PubMed
Alpers to Leigh's encephalopathy Found in trans w/G848S in a 3.5 mo. old female with seizures and Alpers. Post mortem studies revealed Leigh's encephalopathy (Scalais et al., 2012)
PubMed
MNGIE-like Found as a homozygous mutation in a 46 y.o. male with PEO, ptosis, exercise intolerance, peripheral neuropathy, ataxia, and hearing loss (Tang et al., 2012)
PubMed
Torticollis and PEO Found in trans w/W748S in a 43 y.o. female with abnormal gait, ataxia, PEO, and head jerks. (Tuladhar et al., 2012)
PubMed
Parieto-occipital lobe epilepsy Found in trans w/ W748S in a 16 y.o. female with seizures, headaches, cerebellar ataxia, axonal neuropathy, visual impairment, and impaired cognitive function (Roshal et al., 2011)
PubMed
PEO Found in trans w/W748S in a 24 y.o. female with arPEO, cerebellar ataxia, and mtDNA deletions (Lax et al., 2012b)
PubMed
PEO Found in trans w/X1240Q in a 59 y.o. male with arPEO and sensory neuropathy (Lax et al., 2012b)
PubMed
PEO Found in trans w/X1240Q in a 59 y.o. male with arPEO, ptosis and sensory neuropathy (Lax et al., 2012a)
PubMed
PEO Found in trans w/X1240Y in a 42 y.o. Female with arPEO, ptosis and sensory neuropathy (Lax et al., 2012a)
PubMed
PEO Found as a homozygous mutation in a 36 y.o. male with arPEO, ptosis and sensory neuropathy (Lax et al., 2012a)
PubMed
PEO Found in trans w/W748S in a 47 y.o. male with arPEO, ptosis and sensory neuropathy (Lax et al., 2012a)
PubMed
PEO Found in trans w/X1240Y in a 42 y.o. female with PEO, ptosis and sensory neuropathy (Lax et al., 2012a)
PubMed
PEO Found as a homozygous mutation in a 44 y.o. male with arPEO, ptosis and sensory neuropathy (Lax et al., 2012a)
PubMed
PEO Found in trans w/W748S in a 48 y.o. male with PEO, ptosis, ataxia and sensory neuropathy (Lax et al., 2012a)
PubMed
Epilepsy Found in trans w/W748S in a 18 y.o. female with epilepsy, ataxia and sensory neuropathy (Lax et al., 2012a)
PubMed
Epilepsy Found in trans w/W748S in a 20 y.o.female with epilepsy, ataxia and sensory neuropathy (Lax et al., 2012a)
PubMed
Found in a Chinese population with Parkinsonism at an allelic frequency of 0.028 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
PEO Found in compound with G380D in a 63 yo male with cerebellar ataxia, weakness of lower limbs and cognitive impairment Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Alpers Found in compound with T326fs61X in a 4 yo male with mtDNA depletion Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Alpers Found in compound withT914P in a 15 month female with mtDNA depletion Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Epilepsy Found in compound withW748S in a 17 yo female with axonal neuropathy, cerebellar ataxia, and hyperintensity of rolandic, Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Sensorimotor neuropathy Found as a heterozygous mutation in a 60 yo with ALS-like symptoms and mtDNA deletions. Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Encephalopathy Found as a homozygous mutation in 2 teens both had epilepsy, ataxia, and PEO (Tzoulis et al., 2013)
PubMed
Encephalopathy Found as a heterozygous mutation with W748S in 2 patients with PEO and ataxia. (Tzoulis et al., 2013)
PubMed
Encephalopathy Found as a heterozygous mutation with G848S in a patient with epilepsy (Tzoulis et al., 2013)
PubMed
SANDO Found in trans with T251I and P587L in a female in her 60's with a 5 year history of peripheral neuropathy, blurred vision, unstable gait, and sensory ataxia, dementia, and ophthalmoplegia. (Lovan et al., 2013)
PubMed
Epilepsy Found with S1104F in a 5 y.o. male. Patient also had myopathy and ataxia. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. (Sitarz et al., 2014)
PubMed
MIRAS Found with W748S in a 39 y.o. male. Patient also had Ataxia, PEO, and neuropathy. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. (Sitarz et al., 2014)
PubMed
Alpers Found in a 1 y.o female with c.3626_3629dupGATA, located 14nt before the end of exon 22 resulting in the in a premature stop codon and the skipping of most of exon 22. (de Camaret et al., 2014)
PubMed
SANDO Found w/W748S in a 37 y.o. female with ataxia, ptosis, seizures, and mtDNA deletions. (Hanisch et al., 2014)
PubMed
SANDO Found as a homozygous mutation in a 40 y.o. male with ataxia ptosis, and mtDNA deletions. (Hanisch et al., 2014)
PubMed
SANDO Found w/W748S in a 56 y.o. male with ataxia, ptosis, diabetes and mtDNA deletions. (Hanisch et al., 2014)
PubMed
SANDO Found w/W748S in a 45 y.o. male with ataxia, ptosis, diabetes and mtDNA deletions. (Hanisch et al., 2014)
PubMed
SANDO Found w/R627Q in a 50 y.o. male with ataxia, ptosis, diabetes and mtDNA deletions. (Hanisch et al., 2014)
PubMed
Myocerebrohepatopathy Found w/S1095R in a 4 y.o. boy with hypotonia, failure to thrive, and abnormalities in cranial nerve enhancement (Horst et al., 2014)
PubMed
PEO and encephalopathy Found as a homozygous mutation in a 15 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
PEO and encephalopathy Found as a homozygous mutation in a 8 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
PEO and encephalopathy Found as a homozygous mutation in a 16 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Encephalopathy Found w/W748S in a 14 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Encephalopathy Found w/W748S in a 13 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Encephalopathy Found w/G303R in a 9 mo. child w/epilepsy and death at 1.1 yrs. (Tzoulis et al., 2014)
PubMed
Encephalopathy Found w/G303R in a 2 y.o child w/epilepsy, ataxia, and death at 8.0 yrs. (Tzoulis et al., 2014)
PubMed
Encephalopathy Found w/G848S in a 6 mo. child w/epilepsy and death at 6 mo. (Tzoulis et al., 2014)
PubMed
PEO Found in compound w/ M919T in a 23 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
Alpers Found as a homozygous mutation in a 3 y.o. female with seizures, cortical degeneration, hepatic microsteatosis,hippocampal sclerosis, and mtDNA depletion and multiple mtDNA mutations. Carrier frequency in European ancestry of 0.2% to 0.3% (Rajakulendran et al., 2016)
PubMed
MEMSA Found as a homozygous mutation in a 6 y.o. female with encephalitis, occipital lesions, COX-negative muscle fibers and mtDNA deletions and multiple mtDNA mutations. Carrier frequency in European ancestry of 0.2% to 0.3% (Rajakulendran et al., 2016)
PubMed
SANDO Found as a homozygous mutation in a 20 y.o. male with diplopia, axonal neuropathy, ragged red fibers, COX-negative muscle fibers, mtDNA deletions and multiple mtDNA mutations. Carrier frequency in European ancestry of 0.2% to 0.3% (Rajakulendran et al., 2016)
PubMed
MELAS-like Found as a homozygous mutation in a 24 y.o. female with axonal sensory motor neuropathy, ragged red fibers, COX-negative muscle fibers, mtDNA deletions and multiple mtDNA mutations. Carrier frequency in European ancestry of 0.2% to 0.3% (Rajakulendran et al., 2016)
PubMed
Migrains, siezures, and ataxia Found as a compound heterozygote w/ W748S in a 22 y.o. female with epileptic siezures, migrains and ataxia. Her brother presented with siezures at 19 yrs. w/ same mutations. (Vinjam et al., 2015)
PubMed
A study of 68 patients w/ homozygous A467T. Concluded that the clinical presentation was highly variabl, butthat siblings had similar clinical presentations. Attributed the variablitiy to genetic, enviromental, and epigentic factors. (Neeve et al., 2012)
PubMed
MSCA Found in trans withW748S in a 24 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCA Found in trans with W748ST in a 36 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCA Found in trans with W748ST in a 40 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCAE Found in trans with W748S in a16 y.o.with encephalopathy, epilepsy, myopathy, and ataxia. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCAE Found as a homozygous mutation in a 15 y.o.with encephalopathy, epilepsy, SLE, and ataxia. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
Alpers Found as a homozygous mutation in a 3 y.o. girl who had delayed development and epilepsy. (Rajakulendran et al., 2016)
PubMed
MEMSA Found as a homozygous mutation in a 6 y.o. female with sensory axonal peripheral neuropathy, vision impairment,myoclonus, and COX negative fibers. (Rajakulendran et al., 2016)
PubMed
SANDO Found as a homozygous mutation in a 20 y.o. male with diplopia,bilateral ptosis, and sensory peripheral neuropathy. (Rajakulendran et al., 2016)
PubMed
"MELAS-like" Found as a homozygous mutation in a 24 y.o. female with seizure, .deafness, axonal neuropathy, and myopathic weakness. (Rajakulendran et al., 2016)
PubMed
SANDO Found in trans w/W748S with PEO, deafness, migraines, and depression. (Bereau et al., 2016)
PubMed
SCAE Found a homozygous mutation with ataxia, seizures, polyneuropathy, and migraine. (Bereau et al., 2016)
PubMed
SANDO Found in trans w/R597W in a 20 y.o. with ataxia, polyneuropathy, ophthalmoparesis, and dysarthria, (Bereau et al., 2016)
PubMed
PEO Found in trans with T251I and W748S in a 30 y.o. with muscle weaknes and PEO. (Bereau et al., 2016)
PubMed
SANDO Found in trans with R1138C in a 35 y.o. with PEO, ataxia, sensory neuropathy, muscle weakness, and Chorea. (Bereau et al., 2016)
PubMed
SCAE Found in trans with W748S and E1143G in a 36 y.o. with PEO, ataxia, sensory neuropathy, seizures, and migraines. (Bereau et al., 2016)
PubMed
SANDO Found in trans with L559P in a 50 y.o. with PEO, ataxia, sensory neuropathy, dysarthria, dysphagia, and muscle weakness. (Bereau et al., 2016)
PubMed
PEO Found in trans w/T251 and P587L in a 56 y.o. with PEO, muscle weakness, and dysphagia. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/T251I and P587L in a 58 y.o. with ataxia, sensory neuropathy, and dysphagia. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/R275Q in a 62 y.o. with ataxia, sensory neuropathy and PEO. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/T251I and P587L in a 66 y.o. with ataxia, sensory neuropathy, and PEO. (Bereau et al., 2016)
PubMed
SANDO Found in trans w/G848S with ataxia, sensory neuropathy, dysarthria, and PEO. (Bereau et al., 2016)
PubMed
Gait disturbance Found w/ W748S in a 26 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found w/ W748S in a 36 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found as a heterozygote in a 27 y.o. male with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found as a heterozygote in a 12 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found w/W748S in a 49 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Hypoacusis Found as a heterozygote in a 20 y.o. male with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found w/W748S in a 41 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Amino Acid Substitution: N468D
cDNA Position: 1402 a→g (exon 7)
Disease Genetics Frequency Reference
PEO Found in trans w/A1105T in 3 family members w/ PEO (Wanrooij et al., 2004)
PubMed
Microcephaly, cerebellar atrophy, hypotonia, and retinitis pigmentosa Found as a heterozygous mutation in a 15 y.o. female w/ progressive cerebellar atrophy, hypotonia, and retinitis pigmentosa. <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Sensory neuropathy and PEO Heterozygous. Found in 3 related patients. A father with PEO, and a son with cerebellar ataxia and dysphagia, and the father's sister with PEO only (Schulte et al., 2009)
PubMed
Opthmalplegia and peripheral neuropathy Found in trans w/T851A in a 49 y.o. female with ptosis, lower limb weakness, sensory ataxia, gastrointestinal symptoms, and peripheral neuropathy 1 in 322 mitochondrial disease patients (Woodbridge et al., 2012)
PubMed
Amino Acid Substitution: c. 1433 +1g→a
cDNA Position: 1433 ins g→a (Splice variant between ex 7 and ex 8)
Disease Genetics Frequency Reference
Seizures Found in trans w/ A467T in a 2 y.o. w/ hypotonia, encephalopathy, seizures, cardiomyopathy, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: Y479X
cDNA Position: 1433 large del (exon 8)
Disease Genetics Frequency Reference
Reference # rs71653298
PubMed
Amino Acid Substitution: W486X
cDNA Position: 1458 g→a (exon 8)
Disease Genetics Frequency Reference
Parkinsonism and PEO Found in trans w/P587L and T251I. Found in a 68 y.o. female w/ exercise intolerance, PEO, facial diparesis, and left-dominant postural tremor. (Miguel, et al., 2014)
PubMed
Amino Acid Substitution: Q497H
cDNA Position: 1491 g→c (exon 8)
Disease Genetics Frequency Reference
Ataxia Syndrome Found allelic (cis) with W748S + E1143G 1 in 97 found in healthy controls and 1 in 99 found mtDNA disease patients (Winterthun et al., 2005)
PubMed
Alpers, Ataxia Neuropathy In cis with W748S-E1143G. Also found in trans w/G848S, and also in trans w/A467T. (Wong et al., 2008)
PubMed
Alpers In cis w/ W748S and E1143G, and in trans w/ G848S. Found in one child w/ a normal brain MRI (Brunetti-Pierri et al., 2008)
PubMed
Alpers Found in cis with E1143G and W748S, and in trans with A467T in a 6 y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Charcot-Marie Tooth Disease Found w/W748S in a Norweign family with Charcot-Marie Tooth Disease. Total of 245 affected persons from 116 Charcot-Marie tooth disease families in Akershus County Norway. (Hoyer et al., 2014)
PubMed
Amino Acid Substitution: S511N
cDNA Position: 1532 g→a (exon 8)
Disease Genetics Frequency Reference
PEO ad None found in 192 ethnically matched control chromosomes nor in 108 patients with PEO and 140 cases of sporadic PD (Hudson et al., 2006b)
PubMed
Amino Acid Substitution: K512M
cDNA Position: 1535 a→t (exon 8)
Disease Genetics Frequency Reference
Parkinsonism Found as a heterozygous mutation in a 79 yo male with PEO and parkinsonism (Dulhon et al., 2013)
PubMed
Amino Acid Substitution: G517V
cDNA Position: 1550 g→t (exon 8)
Disease Genetics Frequency Reference
Ataxia - neuropathy Found in trans w/ E1143G in a father and his 8 y.o. daughter w/ exercise intolerance, ataxia, and neuropathy. Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Leigh Syndrome Found as a heterozygous mutation in a female pt. w/ dominant ataxia and neuropathy Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation L428P. 19% (9 out of 50) had various mutations in POLG. (Sarzi et al., 2007)
PubMed
Myopathy and micro-cephaly Found in trans w/ D1196N and R1128H (Wong et al., 2008)
PubMed
adPEO Heterozygous, short-stature, Leigh-like disease, neuropathy, stroke, dystonia, chorea, diabetes, myoclonus, Sideroblastic anemia, splenomegaly, Pearson Syndrome to KSS (Wong et al., 2008)
PubMed
Myoclonic epilepsy In trans w/R722H, and in association w/ a mutation in SCN1A, R1645Q (Bolszak et al., 2009)
PubMed
Cerebellar ataxia, dystonia, epilepsy, PEO, hypotonia, mental retardation, and chorea ad, 4 patients ages 4-40 yrs. <0.5% in a Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Seizures, hypoglycemia, myoclonus, hypotonia, and developmental delay Heterozygous, found in 2 half siblings and their unaffected mother (Burusnukul and de los Reyes, 2009)
PubMed
Cerebellar ataxia, PEO, and dysphagia Heterozygous. Found in a 44 yr. old patient (Schulte et al., 2009)
PubMed
Diabetes, strokes, psychosis, and epilepsy Heterozygous. Ad, found in twins, their mother, and grandmother (Hopkins et al., 2009)
PubMed
PEO 56 y.o. male with a heterozygous mutation, and ptosis, myopathy, neuropathy, and mtDNA deletions. (Ferreira et al., 2011)
PubMed
PEO Found as a heterozygous mutation in a 33 y.o. female with PEO and mtDNA deletions. Father also affected. (Ferreira et al., 2011)
PubMed
PEO Found in cis w/ Y955C in a 47 y.o. w/ PEO, ptosis, myopathy, and neuropathy Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures and mitochondrial myopathy Found as a heterozygous mutation in a 56 y.o. woman with mitochondrial myopathy, seizures, ataxia, dysarthria, and dysphonia 1 in 322 mitochondrial disease patients (Woodbridge et al., 2012)
PubMed
Neuronal ceroid lipofuscinosis Maternally inherited heterozygous mutation found with a mutation in CLN5. Infant with hypotonia, bilateral ptosis, and diffuse cerebral atrophy. A 45% reduction in mtDNA compared to controls. (Staropoli et al., 2012)
PubMed
Neutral polymorphism Biochmeical analysis of the recombinant Pol gamma with G517V revealed wild type activity (Kasiviswanathan and Copeland, 2011)
PubMed
Parkinsonism Found in a male 42 y.o. male with a RAB39B variant. Has L- DOPA response, spastic paraparesis, cerebellar dysfunction, and early Parkinsonism. 1of 344 Parkinson patients (M. Guldner, el al. 2016)
PubMed
PEO Found in trans w/Q1236H in a 23 y.o. with PEO and hypostenia. (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: R546C
cDNA Position: 1636 c→t (exon 9)
Disease Genetics Frequency Reference
Neutral polymorphism 1.1% of 450 individuals (GeneSNPs, 2004)
PubMed
Heterozygous with R628Q in one breast tumor (Singh et al, 2009)
PubMed
Reference # rs2307447
PubMed
Amino Acid Substitution: R546S
cDNA Position: 1636 c→a (exon 9)
Disease Genetics Frequency Reference
Reference # rs2307447
PubMed
Amino Acid Substitution: R546G
cDNA Position: 1636 c→g (exon 9)
Disease Genetics Frequency Reference
Reference # rs2307447
PubMed
Amino Acid Substitution: L559P
cDNA Position: 1676 t→c (exon 9)
Disease Genetics Frequency Reference
SANDO Found in trans with L559P in a 50 y.o. with PEO, ataxia, sensory neuropathy, dysarthria, dysphagia, and muscle weakness. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: K561M
cDNA Position: 1882 a→t (exon 9)
Disease Genetics Frequency Reference
Dysmorphy, hypotonia, coloboma, heart failure, and liver insufficiency Compound heterozygosity in cis with W748S Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation K561M in cis with W748S. (Sarzi et al., 2007)
PubMed
Amino Acid Substitution: R562Q
cDNA Position: 1685 g→a (exon 9)
Disease Genetics Frequency Reference
PEO sporadic Not found in 100 DNA samples from healthy Italians (Di Fonzo et al., 2003)
PubMed
Amino Acid Substitution: H569Q
cDNA Position: 1707 c→(a or g) (exon 9)
Disease Genetics Frequency Reference
Hepatocerebral Homozygous (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Amino Acid Substitution: c. 1713-21 T>A
cDNA Position: 1713 -21 (exon 10)
Disease Genetics Frequency Reference
PEO Found in trans w/L304R in a 23 y.o.with PEO, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
Amino Acid Substitution: R574W
cDNA Position: 1720 c→t (exon 10)
Disease Genetics Frequency Reference
PEO Found in trans w/ W312R in a 37 y.o. male patient w/ PEO, dysphagia, and myopathy. Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Liver failure, encephalopathy, and epilepsy Found in trans w/A467T in 2 family members whose parent are unaffected heterozygotes. Kollberg, 2006: Not found in 200 control alleles (Kollberg et al., 2006)
PubMed
Alpers Found in trans w/ A467T (Spinazzola et al., 2009)
PubMed
Alpers Found in trans w/ A467T in 2 pediatric patients w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Progressive ataxia and epilepsy Found in trans w/ L411P in a 69 y.o. female with progressive gait ataxia, dysarthria, and myoclonic jerks. ( Ng et al., 2017)
PubMed
Amino Acid Substitution: R579W
cDNA Position: 1735 c→t (exon 10)
Disease Genetics Frequency Reference
PEO Sporadic / unknown Compound with A889T Not detected in 120 healthy control alleles (Filosto et al., 2003)
PubMed
Amino Acid Substitution: W585X
cDNA Position: 1754 g→a (exon 10)
Disease Genetics Frequency Reference
PEO Found in trans with P648R in a 50 y.o. male with PEO, dysphagia, dysphonia, and parkinsonism with mtDNA deletions (Ferreira et al., 2011)
PubMed
Amino Acid Substitution: P587L
cDNA Position: 1760 c→t (exon 10)
Disease Genetics Frequency Reference
PEO, neuropathy, and hearing loss Found in trans w/ Q1236H in 2 different families and affected siblings Filosto, 2003: not detected in 120 healthy control alleles.  (Filosto et al., 2003) 
PubMed
PEO and mtDNA deletions Found in compound w/T251I/ R807P in1 pt. and w/T251I/ H932Y in a 2nd pt. A 3rd pt. was found in compound w/T251 only. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions. Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians. (Di Fonzo et al., 2003)
PubMed
PEO Found in compound w/T251I and N864S in 2 sisters. Van Goethem, 2003: Not found in 280 control chromosomes. (Van Goethem et al., 2003c)
PubMed
Infantile Hepatocerebral Syndrome Found in compound w/T251I and R232G Ferrari et al., 2005 reported 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. (Ferrari et al., 2005)
PubMed
PEO Found in compound w/T251I and G8484S in a 75 y.o. male     (Kollberg et al., 2005)
PubMed
PEO Found as compound in trans w/ S1176L, G848S, G785X, V1106I, R309L and R227W and cis w/ T251I.  Also, T251I/P587L was found as a homozygous mutation. (Lamantea and Zeviani, 2004) 
PubMed
PEO Found in cis w/T251I and trans w/M603L. Also found in trans w/ R853W (no T251I). All had mtDNA deletions. 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez-Vioque et al., 2006)
PubMed
Alpers Found in cis w/ T251I and in trans w/ G848S, also found as a hetero. mutation with ataxia, ptosis, and neuropathy (Wong et al., 2008)
PubMed
Alpers Found in trans w/R232G and in cis w/T251I. Also, in cis w/P589L and in trans w/W748S. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Alpers Found in cis with T251I with both mutations on each allele. Also, found in cis w/A467T and in trans w/T251I. (Stewart et al., 2009)
PubMed
mtDNA depletion In cis w/T251I and in trans w/E1136K (Taanman et al., 2008)
PubMed
Hepatocerebral MDS Found in cis w/ T251I and in trans w/ R232G (Spinazzola et al., 2009)
PubMed
Restless leg syndrome, ptosis, diplopia, limb weakness, blurred vision Found in trans with T251I. (Aitken, et al., 2009)
PubMed
PEO Found in cis with W748S and in trans with T251I. (Tzoulis, et al., 2009)
PubMed
PEO and mental retardation Found in cis w/ T251I and in trans w/ R275X >0.5% of Dutch population (Blok and van den Bosch et al., 2009)
PubMed
PEO, exercise intolerance, diabetes and a 2nd pt. w/ cataract and myopathy Found in cis w/T251I and in trans w/A467T >0.5% of Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Ptosis Found in cis w/T251I and in trans w/G848S >0.5% of Dutch population (Blok and van den Bosch et al., 2009)
PubMed
PEO, ptosis, epilepsy, mental retardation, ataxia, polyneuropathy, and cataract Ad, in cis w/T251I 3 patients: 4 yr. old w/PEO, ptosis, and motor delay development. A 10 yr. old with epilepsy and mental retardation, and 44 yr. old w/ cataract, polyneuropathy, myopathy, and ataxia >0.5% of Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Seizures, hypotonia, and developmental delay Found w/T251I (Burusnukul and de los Reyes, 2009)
PubMed
Acute disseminated encephalomyelitis Found w/T251I, found in one 4 yr. old patient with autoimmune central nervous system disease (Harris et al., 2010)
PubMed
SANDO Found sporadically w/T251I and G848S in a 80 yr. old male (Weiss and Saneto, 2010)
PubMed
Ptosis and myopathy Found in cis with T251I and in trans with P648R in a 59 y.o. male with dysphagia, dysphonia, myopathy, ptosis, and mtDNA deletions. Father had same symptoms. (Ferreira et al., 2011)
PubMed
PEO Found in cis w/ T251I and in trans w/ H932Y in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Peripheral Neuropathy Found in cis w/ T251I and in trans w/ H932Y in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in cis w/ T251I and in trans w/ G848S in an 80 y.o. w/ peripheral neuropathy, ptosis, and abnormal muscle histology. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in cis w/ T251I and in trans w/ K1191N in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in cis w/ T251I and in trans w/ N1157S in a 9 y.o. Symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ G588D and in cis w/ T251I in a 6 y.o. w/ no symptoms noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
SANDO Found in cis with T251I and in trans with A467T in a female in her 60's with a 5 year history of peripheral neuropathy, blurred vision, unstable gait, and sensory ataxia, dementia, and ophthalmoplegia. (Lovan et al., 2013)
PubMed
SANDO Found in cis w/T251I and in trans w/R869Q in a 34 y.o. female with ataxia, ptosis, diabetes and mtDNA deletions. (Hanisch et al., 2014)
PubMed
PEO Found in compound w/T251I and D1184N in a 33 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
PEO Found in compound w/T251I and D1184N in a 30 y.o. male patient w/ chronic intestinal pseudo-obstruction and PEO. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
Found in compound w/ P116Q and T251I in an Italian 8 y.o. female with fatigue,hypotonia, and delayed psychomotor development with no mtDNA depletion. Diabetic father was positive for P116Q and the deaf mother was positive for T251I and P587L. 0 found in 200 chromosome controls (Scuderi, et al., 2015)
PubMed
Found in compound w/ P116QI and T251I in an Italian 14 y.o. male with fatigue,hypotonia, left eye ptosis, migrains, but normal cognitive skills. Diabetic father was positive for P116Q and the deaf mother was positive for T251I and P587L. 0 found in 200 chromosome controls (Scuderi, et al., 2015)
PubMed
Parkinsonism and PEO Found in cis w/T251I and in trans w/W468X. Found in a 68 y.o. female w/ exercise intolerance, PEO, facial diparesis, and left-dominant postural tremor. (Miguel, et al., 2014)
PubMed
PEO Found in cis with T251I and in trans w/W748S in a 50 y.o.with PEO and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/G848S and in cis w/T251I with PEO, muscle weakness, and cognitive impairment. Similar to SANDO, but no dysarthria. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/S1095R and in cis w/T251I with PEO, muscle weakness, ataxia, and polyneuropathy. Similar to SANDO, but no dysarthria. (Bereau et al., 2016)
PubMed
SANDO Found in trans w/R232H and H227L and in cis w/P587L in a 26 y.o. with PEO, cognitive impairment, ataxia, polyneuropathy, msucle weakness, migraines, dysphagia, and dysarthria. (Bereau et al., 2016)
PubMed
PEO Found in cis with T251I and in trans w/A467T in a 30 y.o. with muscle weaknes and PEO. (Bereau et al., 2016)
PubMed
SANDO Found in cis w/T251I and in trans w/R232H and H277L in a 40 y.o. with PEO, ataxia, polyneuropathy, and dysarthria. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/R852C and in cis w/T251I in a 50 y.o. with PEO, muscle weakness, and polyneuropathy. Similar to SANDO, but no dysarthria. (Bereau et al., 2016)
PubMed
PEO Found in trans w/A467T and in cis w/T251I in a 56 y.o. with PEO, muscle weakness, and dysphagia. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/A467T and in cis w/T251I in a 58 y.o. with ataxia, sensory neuropathy, and dysphagia. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/A467T and in cis w/T251I in a 66 y.o. with ataxia, sensory neuropathy, and PEO. (Bereau et al., 2016)
PubMed
PEO Found in cis w/T251I on both allesls with ptosis and dysphagia (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/T251I and P587L with ataxia, sensory neruopathy, PEO, deafness, and dysphagia. (Bereau et al., 2016)
PubMed
PEO Found in cis with T251I and in trans w/T989dup in a 36 y.o. female with cornieal edema and muscle weakness. One brother affected and has both variants and one unaffected sister with no mutations. Not found in 100 random controls (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: G588D
cDNA Position: 1763 g→a (exon 10)
Disease Genetics Frequency Reference
VPA induced liver failure Found in trans w/ A467T in a 2 y.o. w/ VPA induced liver failure Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ T251I and P587L in a 6 y.o. w/ no symptoms noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: P589L
cDNA Position: 1766 c→t (exon 10)
Disease Genetics Frequency Reference
Alpers Found in cis w/P587L and in trans w/W748S. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Amino Acid Substitution: L591F
cDNA Position: 1774c→t (exon 10)
Disease Genetics Frequency Reference
SANDO Found in trans w/R1096C in a 48 y.o. female with SANDO and dysphagia. (Kurt et al., 2012)
PubMed
Amino Acid Substitution: R597W
cDNA Position: 1789 c→t (exon 10)
Disease Genetics Frequency Reference
PEO with ataxia Homozygous (Stewart et al., 2009)
PubMed
PEO, seizures, and VPA induced liver failure Found as a homozygote in an 18 y.o. with PEO, neuropathy, seizures, and VPA induced hepatotoxicity Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Encephalopathy and ataxia Found in trans w/ A467T in a 26 y.o. w/ encephalopathy, ataxia, neuropathy, and ptosis. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
SANDO Found in trans w/A467T in a 20 y.o. with ataxia, polyneuropathy, ophthalmoparesis, and dysarthria, (Bereau et al., 2016)
PubMed
Amino Acid Substitution: K601E
cDNA Position: 1801 a→g (exon 10)
Disease Genetics Frequency Reference
Sensory axonal neuronopathy Found in a 67 y.o. female and her 61 y.o. brother. Found in compound w/Y837C, D122Y, Q1236H. Both patients have an ataxia, dysarthria, seizures, and sensory neuropathies. Not found in 200 chromosomes controls (Zabalza et al., 2014)
PubMed
Amino Acid Substitution: M603L
cDNA Position: 1807 a→t (exon 10)
Disease Genetics Frequency Reference
PEO with ptosis Found as compound in trans with T251I-P587L 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez-Vioque et al., 2006)
PubMed
Amino Acid Substitution: L605R
cDNA Position: 1814_1815 tt→gc (exon 10)
Disease Genetics Frequency Reference
Alpers Found in trans w/ A467T. Mitochondria depletion in liver (Stewart et al., 2009)
PubMed
Amino Acid Substitution: H613Y
cDNA Position: 1837 c→t (exon 10)
Disease Genetics Frequency Reference
Ptosis Found as a heterozygous mutation in a 14 y.o. male with ptosis, myopathy, severe cerebellar atrophy, dysarthria, and mild cognitive impairment. (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: Y614X
cDNA Position: 1842 c→ a or g
Disease Genetics Frequency Reference
Reference # rs62640033
PubMed
Amino Acid Substitution: R617C
cDNA Position: 1849 c→t (exon 10)
Disease Genetics Frequency Reference
Heterozygous with muscle weakness, exercise intolerance, hearing loss, arrhythmia (Wong et al., 2008)
PubMed
Amino Acid Substitution: L623W
cDNA Position: 1868 t→g (exon 10)
Disease Genetics Frequency Reference
Hypoketotic, hypyoglycaemial, and liver dysfunction Compound heterozygote w/ K755E Not found in 200 healthy controls (Bortot, et al., 2009)
PubMed
Amino Acid Substitution: P625R
cDNA Position: 1874 c→g (exon 10)
Disease Genetics Frequency Reference
Alpers Found as a compound heterozygote w/ A467T in a 1 y.o. with epilepsy and liver failure. (Baruffini et al., 2011)
PubMed
Amino Acid Substitution: R627W
cDNA Position: 1879 c→t (exon 10)
Disease Genetics Frequency Reference
PEO Found in trans w/A467T in a 39 y.o. male whose unaffected parents are hets for each mutation. Van Goethem, 2003: absent in 612 Belgian controls. (Van Goethem et al., 2003a) 
PubMed
PEO Found in trans w/ A467T in 2 PEO patients w/ hearing loss Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Alpers Found in trans w/T914P (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Epilepsy Found in compound with W748S in teenage sisters with epilepsy, encephalitis with mitochondrial abnormalities affecting neurons (Nolte et al., 2013)
PubMed
Amino Acid Substitution: R627Q
cDNA Position: 1880 g→a (exon 10)
Disease Genetics Frequency Reference
Ataxia - myopathy  PEO - ataxia - neuropathy Alpers  Found in cis with Q1236H and in trans with A467T  Found in compound in trans with R309H or R1096H in Alpers  Found in cis with Q1236H and in trans with L965stop-E1143G in PEO (Luoma et al., 2005)
PubMed
Ataxia - myopathy  PEO - ataxia - neuropathy Alpers  Found in cis with Q1236H and in trans with A467T  Found in compound in trans with R309H or R1096H in Alpers  Found in cis with Q1236H and in trans with L965stop-E1143G in PEO Not found in 250 control individuals (Horvath et al., 2006)
PubMed
MELAS Found w/ G848S; heterozygous mutation; w/ mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. (Deschauer et al., 2007)
PubMed
Ataxia Neuropathy Found in cis w/ G11D and in trans w/ R852C. (Wong et al., 2008)
PubMed
Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Found with G848S in a 35 yr. old patient (Schulte et al., 2009)
PubMed
Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Found with T1199X ins. a at c.3594 in a 47 yr. old patient (Schulte et al., 2009)
PubMed
Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Found with R1096C in a 43 yr. old patient (Schulte et al., 2009)
PubMed
Epilepsy and ataxia-neuropathy Found as a compound heterozygote w/S305R in a 5 y.o. with epilepsy that developed ataxia and neuropathy in his teens. (Baruffini et al., 2011)
PubMed
Encephalopathy Found in trans w/ R852C and G11D in a 25 y.o. w/ dementia, encephalopathy, and stroke. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
SANDO Found w/A467T in a 50 y.o. male with ataxia, ptosis, diabetes and mtDNA deletions. (Hanisch et al., 2014)
PubMed
SANDO Found in cis w/Q1236H and in trans w/W748S and E1143G in a 38 y.o. with sensory neuropathy, ataxia, PEO, and cognitive impairment. (Bereau et al., 2016)
PubMed
SANDO Found in cis w/Q1236H and in trans w/W748S and E1143G in a 47 y.o. with sensory neuropathy, ataxia, Ophthalmoparesis and muscle weakness. (Bereau et al., 2016)
PubMed
Gait disturbance Found as a heterozygote in a 61 y.o. male with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found w/G848S in a 29 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
mild ophthalmoparesis Found in trans with G848S in a 33 y.o. male with sensory ataxia and neuroathy (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: R628Q
cDNA Position: 1883 g→a (exon 10)
Disease Genetics Frequency Reference
Mutation found in one breast tumor heterozygous w/ the SNP R546C (Singh et al., 2009)
PubMed
Amino Acid Substitution: P648R
cDNA Position: 1943 c→g (exon 10)
Disease Genetics Frequency Reference
SANDO Found in compound w/R807C in a 39 y.o. patient. (Gago et al., 2006)
PubMed
PEO + myopathy ar, Found as either homozygous mutation or as compound in trans with R1096C in PEO. Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Ptosis and myopathy Found in trans with T251I and P587L in a 59 y.o. male with dysphagia, dysphonia, myopathy, ptosis, and mtDNA deletions. Father had same symptoms. (Ferreira et al., 2011)
PubMed
SANDO Found in trans with R807C in a 49 y.o. pt. with SANDO and mtDNA deletions (Ferreira et al., 2011)
PubMed
PEO Found in trans with W585X in a 50 y.o. male with PEO, dysphagia, dysphonia, and parkinsonism with mtDNA deletions (Ferreira et al., 2011)
PubMed
Parkinsonism and SANDO Found in trans w/R807C ina 52 y.o. male with ptosis, muscle weakness,dysphagia, and SANDO with mtDNA deletions and only 5% COX negative ragged red muscle fibers (Miguel et al., 2014)
PubMed
PEO Found as a homozygous mutation in a 61 y.o. female with dysarthria, dysphagia, cataract, ataxia, polyneuropathy, thyropathy, and upper cerebellar cyst. Patient has mtDNA deletions and ragged red muscle fibers. (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: H659Q
cDNA Position: 1977 c→g (exon 11)
Disease Genetics Frequency Reference
Reference # rs62640030
PubMed
Amino Acid Substitution: E662K
cDNA Position: 1984 g→a (exon 11)
Disease Genetics Frequency Reference
Neutral polymorphism 2.8% of 450 individuals (GeneSNPs, 2004)
PubMed
Amino Acid Substitution: Q666L
cDNA Position: 1997 a→t (exon 11)
Disease Genetics Frequency Reference
Reference # rs62640029
PubMed
Amino Acid Substitution: R709X
cDNA Position: 2125 c→t (exon 12)
Disease Genetics Frequency Reference
PEO Found as compound with T251I. (Del Bo et al., 2003)
PubMed
PEO Found as compound with T251I-P587L in a pt. w/ mtDNA deletions. Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians (Di Fonzo et al., 2003)
PubMed
Amino Acid Substitution: Q715X
cDNA Position: 2143 c→t (exon 12)
Disease Genetics Frequency Reference
Alpers Found in trans w/ A467T (Wong et al., 2008)
PubMed
Encephalopathy Found in trans w/ A467T in a 5 y.o. pt. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: c.2157+5_+6gc>ag
cDNA Position: 2157 gc→ ag (exon 12)
Disease Genetics Frequency Reference
Alpers Found in trans with A467T, most likely a splice site mutation. (Wong et al., 2008)
PubMed
Amino Acid Substitution: R722H
cDNA Position: 2165 g→a (exon 13)
Disease Genetics Frequency Reference
Neutral polymorphism <1 % in control populations (Luoma et al., 2007)
PubMed
Myoclonic epilepsy (Bolszak et al., 2009)
PubMed
PEO, mtDNA deletions and neurological phenotypes Homozygous in 3 siblings with mtDNA deletions, hearing loss, diabetes, dementia, dysphagia, and limb myopathy. Also found in trans w/ W748S in two siblings w/ ptosis, epilepsy, mental retardation 1:135 carrier frequency in a Finnish population (Komulainen et al., 2010)
PubMed
Alpers Found in trans with V1044A in a 2.5 y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Parkinsonism Found in a Chinese population with Parkinsonism at an allelic frequency of 0.033 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
Amino Acid Substitution: H734R
cDNA Position: 2201 a→g (exon 13)
Disease Genetics Frequency Reference
Reference # rs56119329
PubMed
Amino Acid Substitution: N736S
cDNA Position: 2207 a→g (exon 13)
Disease Genetics Frequency Reference
Ataxia, cardiomyopathy, and depression Found in a 52 y.o. female with melancholic depression, unstable gailt, and dilated cardiomyopathy. (Verhoeven et al., 2011)
PubMed
Amino Acid Substitution: G737R
cDNA Position: 2209 g→c (exon 13)
Disease Genetics Frequency Reference
Epilepsy and liver failure Found as compound in trans with A767D in two family members Not found in 250 control individuals (Horvath et al., 2006) 
PubMed
Parkinsonism Parkinsonism in trans with R853W. (Davidzon et al., 2006)
PubMed
Amino Acid Substitution: G737R
cDNA Position: 2210 g→c (exon 13)
Disease Genetics Frequency Reference
Charcot-Marie Tooth disease, (CMT) (profound cerebellar ataxia) Found in trans with the S64L-R232H in CMT. Found in 2/666 (0.3%) of control alleles (Harrower et al, 2008)
PubMed
arPEO+ and Myocerebrohepatopathy (MCHS) Found in trans w/ A467T. In trans w/ E1143G-R943C in MCHS.  Also, found as a single heterozygous mutation. (Wong et al., 2008)
PubMed
PEO Found in trans with W748S. (Tzoulis, et al., 2009)
PubMed
PEO Found in trans w/ L304R in a 54 y.o. with PEO, ptosis, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ G426S in an 11 y.o. w/ seizures and an abnormal MRI Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ V855L in an 8 mo. w/ seizures, liver failure, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans A957V in a 4 mo. No symptoms noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Epilepsy Found with A767D in a 1 y.o. male. Patient also had myopathy. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. (Sitarz et al., 2014)
PubMed
Parkinsonism Found in trans with R853W in a 32 y.o. female with early signs of Parkinsonism and COX negative muscle fibers. Levodopa-responsive. (Rempe et al., 2016)
PubMed
Amino Acid Substitution: N740D
cDNA Position: 2218 a→g (exon 13)
Disease Genetics Frequency Reference
Reference # rs78347903
PubMed
Amino Acid Substitution: V742M
cDNA Position: 2224 g→a (exon 13)
Disease Genetics Frequency Reference
SNP Reference # rs147827654
PubMed
Amino Acid Substitution: G746S
cDNA Position: 2236 g→a (exon 13)
Disease Genetics Frequency Reference
Ataxia, PEO ar, Found in cis w/ E1143G, and in trans G848S 1in 454 alleles (Stewart et al., 2009)
PubMed
PEO Found in trans w/G848S in a 36 y.o. male with PEO, peripheral neuropathy, and ataxia (Lax et al., 2012a)
PubMed
Amino Acid Substitution: W748C
cDNA Position: 2244 g→t (exon 13)
Disease Genetics Frequency Reference
MELAS Found in trans w/ R309C in an 18 y.o. female with seizues, vision loss, neuropathy, ophthalmoparesis. Each parent is an unaffected heterozygote. (Ching-wan et al., 2015)
PubMed
Amino Acid Substitution: W748S
cDNA Position: 2243 g→c (exon 13)
Disease Genetics Frequency Reference
Ataxia Found in compound w/E1143G w/ataxia, dysarthria, and cognitive impairment. Also found as a homozygous mutation. (Van Goethem et al., 2004) 
PubMed
Alpers Found in compound w/ Y1210fs1216X and E1143G Ferrari et al., 2005 reported 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. (Ferrari et al., 2005)
PubMed
Hepatocerebral Syndrome Found in 4 children in cis w/E1143G and in trans w/G848S. (Davidzon et al., 2005)
PubMed
Ataxia Found as a homozygous mutation w/ E1143G Carrier frequency in the general Finnish population of 1:125 from 500 control chromosomes (Hakonen et al., 2005)
PubMed
Alpers Found in trans w/E1143G and in cis w/G848S in a 13 mo. old male (Nguyen et al., 2005)
PubMed
Ataxia Syndrome Found in trans w/Q497H in patients w/ progressive ataxia and epilepsy 1 in 97 found in healthy controls and 1 in 99 found mtDNA disease patients (Winterthun et al., 2005) 
PubMed
PEO Found in trans w/A467T and also in trans w/ Q308H Not found in 250 control individuals (Horvath et al., 2006)
PubMed
SCAE Found in trans w/L304R in a 20 y.o. female w/ spinocerebellar ataxia epilepsy syndrome and mtDNA deletions Not found in 300 healthy French control chromosomes (Naimi et al., 2006)
PubMed
PEO, ataxia, and epilepsy Found as a homozygous mutation in 13 pts. ranging in age from 2 to 19 yrs. One heterozygous 55 y.o. pt. with epilepsy. Also found in trans w/A467T in 7 pts. Ranging in age from 14 to 36 yrs. All w/ wide spectrum of mitochondrial disease. Studied in 26 mitochondrial disease patients (Tzoulis et al., 2006)
PubMed
Ataxia Neuropathy A biochemical study of W748S pol gamma which exhibited low DNA polymerase activity, low processivity and a severe DNA-binding defect, and is commonly found in cis w/E1143G (Chan et al., 2006) 
PubMed
Alpers Found in cis w/K561M and found in cis with E1143G. Both patients had mtDNA depletion Sarzi, et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation W748S with E1143G. (Sarzi, et al. 2007)
PubMed
Alpers, Ataxia Neuropathy, and arPEO+ Found in trans w/ G848S, and in cis w/ Q479H-E1143G. Also found in trans w/ A467T. arPEO+ as a compound w/ E1143G (Wong et al., 2008)
PubMed
Alpers Homozygous, juvenile onset (Uusimaa et al., 2008)
PubMed
Alpers Found in trans w/ [R852C and G11D], and found in 2 additional pts. in trans w/T914P. Found homozygous in one pt. Found in trans w/ G848S. Found in trans w/[P587L and P589L]. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
PEO and Alpers Found in trans w/ A467T. In a 2nd pt., found in cis w/ E1143G and in trans w/ G11D and R852C. (Stewart et al., 2009)
PubMed
Alpers In cis w/E1143G and in trans w/ G484S (Taanman et al., 2008)
PubMed
mtDNA depletion In cis w/E1143G and in trans w/ H1110Y and Q1236H (Taanman et al., 2008)
PubMed
Alpers In cis w/ Q497H and E1143G, and in trans w/ G848S Found in one child w/ a normal brain MRI (Brunetti-Pierri et al., 2008)
PubMed
Alpers Found in 2 infants in trans w/ Y1210X (Spinazzola et al., 2009)
PubMed
Alpers Found in trans w/ L244P (Spinazzola et al., 2009)
PubMed
Alpers Found in trans w/ D930N (Spinazzola et al., 2009)
PubMed
Parkinsonism Homozygous mutation w/ PEO, ataxia, peripheral neuropathy, and hearing loss (Remes et al., 2009)
PubMed
Leigh Syndrome Found in trans with G11D and R852C (Naess, et al., 2009)
PubMed
PEO Found in trans with G737R, and in a 2nd pt. in cis with P587L and in trans with T251I. (Tzoulis, et al., 2009)
PubMed
PEO, ptosis, polyneuropathy, ataxia, and dysartria Found in trans w/A467T and in compound w/ E1143G <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Epilepsy, myoclonus, polyneuropathy, ataxia, and cognitive delay; a 2nd pt. with epilepsy and MELAS-like symptoms Found in trans w/ A467T. <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Found with A467T in 4 middle aged patients, 2 of which are sisters (Schulte et al., 2009)
PubMed
Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Homozygous in a 39 yr. old patient (Schulte et al., 2009)
PubMed
Hepatocerebral - Alpers symptoms Found w/P1073L. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility (Kurt et al., 2010)
PubMed
SANDO Found in trans w/ P1073L. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility (Posada et al., 2010)
PubMed
PEO, mtDNA deletions and neurological phenotypes Found in trans with A467T and in cis with E1143G. Sensory ataxia, dysarthria, and opthalmoplegia. 1:135 carrier frequency in a Finnish population (Komulainen et al., 2010)
PubMed
Alpers Homozygous in 3 siblings with mtDNA deletions, hearing loss, diabetes, dementia, dysphagia, and limb myopathy. Also found in trans w/ R722H in two siblings w/ Ptosis, epilepsy, mental retardation 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Alpers Found in cis with E1143G and in trans with R807C in a 1 y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Alpers Found in cis with E1143G and Q497H, and in trans with A467T in a 6 y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Alpers Found in cis with E1143G and in trans with G848S in a 11 mo. old with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Alpers Found in cis with 1143G and in trans with T914P in a 2.5 y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Ataxia and cerebellar atrophy Found as a homozygote in a 30 y.o. pt. with peripheral neuropathy, ataxia, and fatigability Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
SANDO and PEO Found in trans w/ A467T in a 54 y.o. with PEO, ptosis, ataxia, neuropathy, and SANDO Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A467T in a 16 y.o. with seizures, dystonia, choria, neuropathy, and ptosis Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in a 25 y.o. pt. that is homozygous for the W748S mutation and S28C as a heterozygote with PEO, ataxia, ptosis, and hearing loss Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ D892fsX39 in a 9 mo. old pt. w/ a deceased sibling Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ G848S in a 5 y.o. pt. w/myclonic seizures, liver failure, and hypotonia Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Alpers Found in trans w/ Q449X in a 21 y.o. with seizures Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ G848S in a 7 y.o. w/ seizures and cortical blindness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ G848S in a 3 y.o. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ G8484S in a 6 y.o. pt. with GI issues and irregular occipital lobe. Sibling died from VPA induced organ failure. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/A467T in an 18 y.o. with ataxia, seizures, dystonia, and optic atrophy. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in trans w/ R953C in a 51 y.o. w/ peripheral neuropathy, ptosis, hypotonia, ataxia, and seizures. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ T914P in a 5 y.o. w/ seizures Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ T914P in an 8 mo. w/ seizures, hypotonia, abnormal MRI, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ A467T in a 29 y.o. symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures and liver failure Found in trans w/ M797del in a 1 y.o. with seizures and hepatic failure Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures and liver failure Found in trans w/ G888D in a 2 y.o. w/ seizures, hepatic failure, ketosis and abnormal MRI Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Alpers Found in trans w/ R852H in a 3 y.o. w/ Alpers Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
MSCAE Found in trans w/ T914P in a 15 y.o. female with mitochondrial spinocerebellar ataxia and epilepsy. (Hinnell et al., 2012)
PubMed
Alpers Found in trans w/G848S in a 6 yr. 4 mo. with microvesicular fatty changes of the liver, myclonic seizures, and ataxia (Hunter et al., 2011)
PubMed
Alpers found in trans w/G8484S in a 6 yr. 9 mo. with seizures, developmentally delayed, and ataxia. (Hunter et al., 2011)
PubMed
Alpers Found w/ E1143G and R232H in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Alpers Found w/M1163R and E1143G in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
MNGIE-like Found in a 25 y.o. female as a homozygous mutation. Patient had migraines, ptosis, PEO, exercise intolerance, peripheral neuropathy, and ataxia. (Tang et al., 2012)
PubMed
MNGIE-like Found in compound with R953C in a 50y.o. male with cognitive impairment, muscle weakness, diarrhea, vomiting, ptosis, and opthalmoparesis. (Tang et al., 2012)
PubMed
Alpers and PEO Found in trans with R852C in a pediatric female patient with hypotonia, developmental delay, ataxia, and seizures (Vasta et al., 2012)
PubMed
MIRAS Mother and son were homozygous for E1143G in cis with E1143, and the unaffected father was heterozygous for W748S in cis with E1143G. Both mother and son had decreased mtDNA and spinocerebellar ataxias with presentation in late 30's and early 40's. Frequencies in Europe for W748S+E1143G or A467T range from 0.6% in Belgium, 0.8% in Finland, and 2% in Finland (Palin et al., 2012)
PubMed
Torticollis and PEO Found in trans w/A467T in a 43 y.o. female with abnormal gait, ataxia, PEO, and head jerks. (Tuladhar et al., 2012)
PubMed
Parieto-occipital lobe epilepsy Found in trans w/ A467T in a 16 y.o. female with seizures, headaches, cerebellar ataxia, axonal neuropathy, visual impairment, and impaired cognitive function (Roshal et al., 2011)
PubMed
PEO Found in trans w/A467T in a 24 y.o. female with arPEO, cerebellar ataxia, and mtDNA deletions (Lax et al., 2012b)
PubMed
PEO Found in trans w/ R1096C in a 49 y.o. male with PEO, ptosis, epilepsy and peripheral neuropathy (Lax et al., 2012a)
PubMed
PEO Found in trans w/ A467T in a 47 y.o. male with arPEO, ptosis and sensory neuropathy (Lax et al., 2012a)
PubMed
PEO Found in trans w/A467T in a 48 y.o. male with PEO, ptosis, ataxia and sensory neuropathy (Lax et al., 2012a)
PubMed
Epilepsy Found in trans w/A467T in a 18 y.o.female male with epilepsy, ataxia and sensory neuropathy (Lax et al., 2012a)
PubMed
Epilepsy Found in trans w/A467T in a 20 y.o. female male with epilepsy, ataxia and sensory neuropathy (Lax et al., 2012a)
PubMed
Found in a Chinese population with Parkinsonism at an allelic frequency of 0.391 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
Epilepsy Found in compound with R627W in teenage sisters with epilepsy, encephalitis with mitochondrial abnormalities affecting neurons (Nolte et al., 2013)
PubMed
PEO Found in compound with L304R in a 27 yo female with sensory and cerebellar ataxia, axonal sensory neuropathy Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Epilepsy Found in compound with A467T in a 17 yo female with axonal neuropathy, cerebellar ataxia, and hyperintensity of rolandic, Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Epilepsy Found in compound with T914P in a 6 yo male with epilepsy and hepatic cholestasis and cytolysis, and mtDNA deletions Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
SANDO Found as a homzygous mutation in a 37 yo male with SANDO, parkinsonism, and mtDNA deletions Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Epilepsy Found as a heterozygous mutation in a 2 yo female with epilepsy, delayed psychomotor development, and mtDNA deletions and depletion. Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Encephalopathy Found as a heterozygous mutation with A467T in 2 patients with PEO and ataxia. (Tzoulis et al., 2013)
PubMed
Encephalopathy Found as a homozygous mutation in 7 patients with ataxia, epilepsy, and PEO (Tzoulis et al., 2013)
PubMed
Epilepsy Found with deletion of a" t" at c.3600 in a 3 y.o. female. Patient also had myopathy. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. (Sitarz et al., 2014)
PubMed
MIRAS Found with A467T in a 39 y.o. male. Patient also had Ataxia, PEO, and neuropathy. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. (Sitarz et al., 2014)
PubMed
MIRAS Found as a homozygous mutation in a 36 y.o. male with Ataxia, neuropathy, and PEO. . In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid (Sitarz et al., 2014)
PubMed
Alpers Found w/E1143G in a 16 mo. boy with epilepsy, mtDNA depletion, and noted defects of the respiratory chain complexes I,II, and IV. (de Camaret et al., 2014)
PubMed
Charcot-Marie Tooth Disease Found w/Q497H in a Norweign family with Charcot-Marie Tooth Disease. Total of 245 affected persons from 116 Charcot-Marie tooth disease families in Akershus County Norway. (Hoyer et al., 2014)
PubMed
SANDO Found w/A467T in a 37 y.o. female with ataxia, ptosis, seizures, and mtDNA deletions. (Hanisch et al., 2014)
PubMed
SANDO Found w/A467T in a 56 y.o. male with ataxia, ptosis, diabetes, and mtDNA deletions. (Hanisch et al., 2014)
PubMed
SANDO Found w/A467T in a 56 y.o. male with ataxia, ptosis, diabetes and mtDNA deletions. (Hanisch et al., 2014)
PubMed
SANDO Found w/A467T in a 45 y.o. male with ataxia, ptosis, diabetes and mtDNA deletions. (Hanisch et al., 2014)
PubMed
Encephalopathy and PEO Found as a homozygous mutation in a 6 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Encephalopathy Found as a homozygous mutation in a 15 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Encephalopathy and PEO Found as a homozygous mutation in a 17 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Encephalopathy and PEO Found as a homozygous mutation in a 12 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Encephalopathy Found as a homozygous mutation in a 2 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Encephalopathy and PEO Found as a homozygous mutation in a 16 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Encephalopathy and PEO Found as a homozygous mutation in a 15 y.o. w/epilepsy, ataxia, and neuropathy (Tzoulis et al., 2014)
PubMed
Alpers Found as a heterozygous mutation with the 2nd POLG1 allel completely deleted. The patient was a 2 y.o. Swedish male with impaired motor skills, epileptic seizure, and died from VPA induced liver failure. (Naess, et al., 2011)
PubMed
PEO Found in compound w/A143V and E1143G in a 40 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
Hypertrophic olivary degeneration Found as a homozygous mutattion in a 30 y.o. male with hepatitis C and hearing loss, slurred speech, gait ataxia (Arkadir et al., 2015)
PubMed
Progressive ataxia and Palatal tremor (PAPT) Found in trans w/I1185N in a 52 y.o. male w/ kinetic and static ataxia, dysarthria, palatal trmor, and vertical nystagmus. (Nicastro et al., 2016)
PubMed
Migrains, siezures, and ataxia Found as a compound heterozygote w/ A467T in a 22 y.o. female with epileptic siezures, migrains and ataxia. Her brother presented with siezures at 19 yrs. w/ same mutations. (Vinjam et al., 2015)
PubMed
fragile X tremor/ataxia syndrome (FXTAS) Found as a homozygous mutation in a 60 y.o. Swedish male with balance and gait difficulties, slurred speech, diplopia and cognitive decline. Negative for Fragile X Syndrome. (Paucar et al., 2016)
PubMed
Ataxia neuropathy Found as a homozygote in a 29 y.o. women with PEO, general areflexia, and abnormal leg pallesthesia. MRI showed lesions in the thalamus, cerebellum, and inferior olivary nucleus. ( Henao et al., 2016)
PubMed
PEO Found in trans with T251I and P587L in a 50 y.o.with PEO and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCA Found as a homozygote in a 16 y.o.with encephalopathy, Epilepsy, SLE, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCAE Found as a homozygote in a 12 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCAE Found as a homozygote in a 17 y.o.with encephalopathy, Epilepsy, SLE, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCA Found in trans with A467T in a 24 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCA Found in trans with A467T in a 36 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCA Found in trans with A467T in a 40 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
MSCAE Found in trans with A467T in a16 y.o.with encephalopathy, epilepsy, SLE, and ataxia. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. (Tzoulis et al., 2016)
PubMed
SANDO Found in trans w/A467T with PEO, deafness, migraines, and depression. (Bereau et al., 2016)
PubMed
SCAE Found in trans w/E1143G on both allels in a 22 y.o. with cerebellar ataxia, seizures, deafness, migraines, and dystonia (Bereau et al., 2016)
PubMed
SCAE Found in trans w/L304R with PEO, cognitive impairment, seizures, ataxia, polyneuropathy, dysphagia, and dysarthria. (Bereau et al., 2016)
PubMed
SCAE Found in trans with A467T and in cis E1143G in a 36 y.o. with PEO, ataxia, sensory neuropathy, seizures, and migraines. (Bereau et al., 2016)
PubMed
SANDO Found as a homozygous mutation in a 37 y.o. with Parkinsonism, sensory neuropathy, ataxia, and PEO. (Bereau et al., 2016)
PubMed
SANDO Found in cis w/E1143G and in trans w/ R627Q and Q1236H in a 38 y.o. with sensory neuropathy, ataxia, PEO, and cognitive impairment. (Bereau et al., 2016)
PubMed
SANDO Found in trans w/R627Q and Q1236H and in cis w/E1143G in a 47 y.o. with sensory neuropathy, ataxia, Ophthalmoparesis and muscle weakness. (Bereau et al., 2016)
PubMed
SANDO Found as a homozygous mutation in a 50 y.o. with sensory neuropathy, ataxia, cognitive impairment and PEO. (Bereau et al., 2016)
PubMed
Gait disturbance Found w/ A467T in a 26 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found w/ A467T in a 36 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found as a heterozygote in a 22 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found w/A467T in a 49 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found as a heterozygous mutation in a 29 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Gait disturbance Found w/A467T in a 41 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
PEO Found in trans with A847T in a 49 y.o. male with muscle weakness and sensory neuropathy. Patient has mtDNA deletions, COX negative muscle fibers, and ragged red fibers. (Pozzo et al., 2017)
PubMed
Cerebellar ataxia and sensory neuropathy Found as a homozygous mutation in a 40 y.o. male with dysphagia, ataxia, neuropathy, and loss of vibration sense dysarthria (Pozzo et al., 2017)
PubMed
Ataxia Found as a homozygous mutation in a 60 y.o. Swedish male with balance and gait difficulties, slurred speech, diplopia and cognitive decline. Negative for Fragile X Syndrome. (Paucar et al., 2016)
PubMed
Ataxia and palatal tremor Found in trans with I1185N in a 52 y.o. male with diabetes, hypertension, and progressive gait and balance difficulties (Nicastro et al., 2016)
PubMed
Amino Acid Substitution: F749S
cDNA Position: 2246 t→c (exon 13)
Disease Genetics Frequency Reference
Alpers Found in compound with A467T Not found in 300 control chromosomes (Nguyen et al., 2006)
PubMed
PEO Found in trans w/ c.3104 +3a→t in a 66 y.o. w/ PEO, ptosis, myopathy, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A467T in a 6 y.o. w/ seizures Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ A467T in an 8 mo. symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Optic atrophy Found in trans w/c.3104+3A>T in a 65 y.o. male with ptosis, dysphagia, exercise induced myalgia, limb weakness, and diabetes. (Milone et al., 2011)
PubMed
Amino Acid Substitution: L752P
cDNA Position: 2255 t→c (exon 13)
Disease Genetics Frequency Reference
Epilepsy, seizures, VPA induced liver failure Found in trans w/W748S and E1143G (Zsurka, et al., 2008)
PubMed
Inclusion body myositis Found as a heterozygous mutation in a Swedish patient with Inclusion body myostitis. In addition the patient had COX deficient muscle fibers, ragged red fibers, and mtDNA deletions. 1 in 26 patients with inclusion body myositis. 8 of which had heterozygous POLG mutations. (Lindgen et al., 2015)
PubMed
Amino Acid Substitution: H754Q
cDNA Position: 2262 c→g (exon 13)
Disease Genetics Frequency Reference
Seizures and hepatic failure Found in trans w/ A467T in 2 y.o. w/ seizures, hepatic failure, cerebellar atrophy, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: K755E
cDNA Position: 2263 g→a (exon 13)
Disease Genetics Frequency Reference
Hypoketotic, hypyoglycaemial, and liver dysfunction Compound heterozygote w/ L623W Not found in 200 healthy controls (Bortot, et al., 2009)
PubMed
Amino Acid Substitution: G763R
cDNA Position: 2287 g→c (exon 14)
Disease Genetics Frequency Reference
MNGIE-like Found as a homozygous mutation in a 17 y.o. with PEO, polyneuropathy,and gastro-intestinal dysmotility (Bereau et al., 2016)
PubMed
PEO, SANDO ar, Found as a homozygous mutation in PEO-SANDO Not found in 500 ethnically-matched control chromosomes (Santoro et al., 2006)
PubMed
Amino Acid Substitution: P765T
cDNA Position: 2293 c→a (exon 14)
Disease Genetics Frequency Reference
Ataxia neuropathy spectrum and gastroparesis Found as a homozygous mutation in a 52 y.o. woman with ptosis, ataxia neuropathy, gastroparesis, and opthalmoplegia (Bostan et al., 2012)
PubMed
Amino Acid Substitution: A767D
cDNA Position: 2300 c→a (exon 14)
Disease Genetics Frequency Reference
Alpers Found as compound in trans with G737R Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Epilepsy Found with G737R in a 1 y.o. male. Patient also had myopathy. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. (Sitarz et al., 2014)
PubMed
Amino Acid Substitution: K768E
cDNA Position: 2302 a→g (exon 14)
Disease Genetics Frequency Reference
neuropathy and ataxia Found in compound with M464T in a teenage female with axonal sensorimotor neuropathy and sensory ataxia with multiple mtDNA deletions Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Amino Acid Substitution: G785fs21X
cDNA Position: 2354 ins g stop @ 806 (exon 14)
Disease Genetics Frequency Reference
PEO ar, Compound with T251I Absent in 100 control DNA samples (Lamantea et al., 2002)
PubMed
Amino Acid Substitution: R790H
cDNA Position: 2369 g→a (exon 14)
Disease Genetics Frequency Reference
SNP Reference # rs191490663 4 in 10,000 individuals are heterozygous w/WES data. 1.82% in Puerto Rican population
PubMed
Alpers Found as a heterzygous mutation in one patient w/Alpers 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: M797del
cDNA Position: 2391-2393 gat de (exon 14)
Disease Genetics Frequency Reference
Seizures and liver failure Found in trans w/ W748S in a 1 y.o. with seizures and hepatic failure Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: A804T
cDNA Position: 2410 g→a (exon 14)
Disease Genetics Frequency Reference
Fatigue, muscle complaints, and bulbar dysarthria ar, found in one 55 yr. old pt. <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Amino Acid Substitution: R807H
cDNA Position: 2420 g→a (exon 14)
Disease Genetics Frequency Reference
Seizures and hepatic failure Found in trans w/ A467T in a 1 y.o. with seizures, hepatic failure, hypotonia, and failure to thrive Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: R807P
cDNA Position: 2420 g→c (exon 14)
Disease Genetics Frequency Reference
PEO Sporadic Compound with T251I (Del Bo et al., 2003)
PubMed
PEO Found in compound w/T251I/ P587L in1 pt. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions. Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians (Di Fonzo et al., 2003)
PubMed
Amino Acid Substitution: R807C
cDNA Position: 2419 c→t (exon 14)
Disease Genetics Frequency Reference
SANDO Found in compound w/P648R in a 39 y.o. patient. (Gago et al., 2006)
PubMed
Alpers Found in trans with E1143G and W748S in a 1 y.o. with epilepsy and Encephalopathy (Isohanni et al., 2011)
PubMed
Ptosis and myopathy Found as a heterozygous mutation in a 74 y.o. male with myopathy, ptosis, and diplopia (Ferreira et al., 2011)
PubMed
SANDO Found in trans with P648R in a 49 y.o. pt. with SANDO and mtDNA deletions. (Ferreira et al., 2011)
PubMed
Liver failure Found in trans w/ A467T in a 1 y.o. w/ encephalopathy, liver failure, and lactic acidosis Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Parkinsonism and SANDO Found in trans w/P648R ina 52 y.o. male with ptosis, muscle weakness,dysphagia, and SANDO with mtDNA deletions and only 5% COX negative ragged red muscle fibers (Miguel et al., 2014)
PubMed
Amino Acid Substitution: 4.7kb deletion of exons 15-21
cDNA Position: Intronic deletion starting in intron 14 (87,662,154) thru intron 21 (87,666,650), excising exons 15-21.
Disease Genetics Frequency Reference
Alpers Found as a compound heterozygote w/ A467T. Patient had early on set of Alpers and died at the age of 3.5 y.o.. The father carried the A467T mutation, and the mother the deletion. (Compton et al., 2010)
PubMed
Alpers Found as a compound heterozygote w/ A467T in a 3.5 y.o. The father carried the A467T mutation, and the mother the deletion. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al. 2011)
PubMed
Alpers Found in trans w/A467T in a 2 y.o. w/seizures, developmentally delayed, and ataxia (Hunter et al., 2011)
PubMed
Amino Acid Substitution: c. 2480+1g>a
cDNA Position: 2480+1 g→a splice site (exon 15)
Disease Genetics Frequency Reference
Alpers Found in trans w/ W748S-E1143G (Wong et al., 2008)
PubMed
Amino Acid Substitution: IVS15-9- c.2485del 12bp
cDNA Position: 2485 del 12bp (exon 16)
Disease Genetics Frequency Reference
Alpers Splice site mutation 3'exon15/intron junction, Found in trans with A467T Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Amino Acid Substitution: IVS16-10 c>t
cDNA Position: IVS16-10 c>t (exon 16)
Disease Genetics Frequency Reference
Cerebellar ataxia, sensory neuropathy, and dysphagia Homozygous. Found in a 60 y.o. patient (Schulte et al., 2009)
PubMed
Amino Acid Substitution: Y831F
cDNA Position: 2492 a→t (exon 16)
Disease Genetics Frequency Reference
Reference # rs41549716
PubMed
Amino Acid Substitution: Y831S
cDNA Position: 2492 a→c (exon 16)
Disease Genetics Frequency Reference
Reference # rs41549716
PubMed
Amino Acid Substitution: Y831C
cDNA Position: 2492 a→g (exon 16)
Disease Genetics Frequency Reference
Epilepsy, exericise intolerance, and hearing loss Found in a 6 y.o. female with mtDNA deletions in muscle tissue. The patient, her mother and her grand mother, but not her sister, had a heterozygote Y831C mutation. Analysis by mispairing PCR showed the pres- ence of mutation Y831C in 57% of 87 controls. (Barthelemy et al., 2002)
PubMed
PEO, neuropathy, and parkinsonism Found as a heterozyous mutation in a 49 y.o woman with parkinsonism, PEO, and mtDNA deletions. Her 59 y.o. brother was heterozygous for Y831C with overt parkinsonian features. Mancuso 2004: Not seen in 120 control subjects  (Mancuso et al., 2004b) 
PubMed
The allelic discrimination technology proposed here for the identification of the mutation causing the Y831C substitution is amenable to high-throughput genotyping an thus is well suited to both extensive population studies and molecular diagnostics. Stopinska 2006: present in the Polish population at a frequency of 2.25%.  (Stopinska et al., 2006)
PubMed
Neutral polymorphism Studied POLG1 in 140 UK patients with idiopathic Parkinson disease (PD) and 279 Italian patients with PD and compared them to a UK control group (n = 207) and an Italian control group (n = 285). Our observations do not support a role for common POLG1 genetic variants in PD and indicate that dominant POLG1 mutations are a rare cause of parkinsonism in the general population. Tiangyou 2006: Found at the same frequency in age-matched controls.  (Tiangyou et al., 2006)
PubMed
Neutral polymorphism Found several amino acid substitutions, none of them associating with PD. These included a previously parkinsonism-associated POLG variant Y831C, found in one patient with PD, but also in five controls, suggesting that it is a neutral amino acid polymorphism. The coding region of POLG1 was analyzed in 140 Finnish patients with PD and their 127 spouses as age- and ethnically matched controls. (Luoma et al., 2007)
PubMed
Heterozygous, hypotonia, Autism, neuropathy, ataxia, hearing loss, short stature, muscle weakness, fatigue (Wong et al., 2008)
PubMed
mtDNA depletion In trans w/ H1134R (Taanman et al., 2008)
PubMed
mtDNA deletions and seizures Heterozygous mutation found in a 34 y.o. woman with seizures, opthalmoparesis, ptosis,, peripheral neuropathy….. 2 in 322 mitochondrial disease patients (Woodbridge et al., 2012)
PubMed
Muscle weakness Heterozygous mutation found in a 46 y.o. woman with proximal weakness and myagia, and muscle twitches. 2 in 322 mitochondrial disease patients (Woodbridge et al., 2012)
PubMed
Found in a Chinese population with Parkinsonism at an allelic frequency of 0.034 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
Amino Acid Substitution: Y837C
cDNA Position: 2510 a→g (exon 16)
Disease Genetics Frequency Reference
Sensory axonal neuronopathy Found in a 67 y.o. female and her 61 y.o. brother. Found in compound w/K601E, D122Y, Q1236H. Both patients have an ataxia, dysarthria, seizures, and sensory neuropathies. Not found in 200 chromosomes controls (Zabalza et al., 2014)
PubMed
Amino Acid Substitution: Y831C
cDNA Position: 2510 a→g (exon 16)
Disease Genetics Frequency Reference
myopathy Found as a heterozygous mutation in a 77 y.o. male with neck extensor muscles myopathy and mtDNA deletions (Pozzo et al., 2017)
PubMed
Ptosis Found as a heterozygous mutation in a 61 y.o. female with ptosis, thyropathy, hearing loss, and mtDNA deletions (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: A847T
cDNA Position: 2539 g→a (exon 16)
Disease Genetics Frequency Reference
PEO Found in trans with T748Sin a 49 y.o. male with muscle weakness and sensory neuropathy. Patient has mtDNA deletions, COX negative muscle fibers, and ragged red fibers. Not found in 100 controlsA847T (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: G848S
cDNA Position: 2542 g→a (exon 16)
Disease Genetics Frequency Reference
PEO Compound with T251I Lamantea, 2002: absent in 100 control DNA samples (Lamantea et al., 2002) 
PubMed
Alpers Found in compound w/A467T in a 6 mo. male w/ Ferrari et al., 2005 reported 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. (Ferrari et al., 2005) 
PubMed
Alpers Found as compound W748S/E1143G. (Davidzon et al., 2005)
PubMed
PEO Compound with T251I and P587L in a 75 y.o. male  (Kollberg et al., 2005)
PubMed
Alpers Found as compound in Alpers with A467T and also in trans w/ W748 /E1143G. (Nguyen et al., 2005)
PubMed
Alpers Found as compound in Alpers with A467T in a 6 mo. female de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder (de Vries et al., 2007)
PubMed
Alpers Found as compound with A467T in a 6 mo. female w/ liver failure and encephalopathy Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Liver failure, encephalopathy, and epilepsy Found as compound with A467T in a 3 mo. male w/ liver failure and encephalopathy Not found in 200 control alleles   (Kollberg et al., 2006)
PubMed
MELAS Found w/ R627Q; heterozygous mutation; w/ mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. (Deschauer et al., 2007)
PubMed
Alpers Found in trans with A467T, Q497H, W748S, and E1143G. Also found in trans w/ T251I-P587L. (Wong et al., 2008)
PubMed
Alpers Found in trans w/W748S, and in a 2nd pt. in trans w/A467T. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
PEO and Ataxia In trans w/ G746S and E1143G. Also found in trans w/ A467T. Found in one child with a normal brain MRI. (Stewart et al., 2009)
PubMed
Leigh Syndrome In trans w/R232H (Taanman et al., 2008)
PubMed
Alpers In trans w/E1143G +W748S (Taanman et al., 2008)
PubMed
Alpers Found in trans w/ Q497H, W748S, and E1143G. (Brunetti-Pierri et al., 2008)
PubMed
Myopathy and gastrointestinal obstruction Found in trans w/ R227W with mtDNA depletion and Cox deficient muscle fibers (Giordano et al., 2009)
PubMed
mtDNA depletion Found in trans with A467T (Roels, et al., 2009)
PubMed
Ptosis ar, found in trans w/ T251I+P587L <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Found with R627Q in a 35 yr. old patient (Schulte et al., 2009)
PubMed
Alpers Found in trans with A467T (Hasselmann et al., 2009)
PubMed
Hepatocerebral - Alpers symptoms Found in trans w/P1073L. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility (Kurt et al., 2010)
PubMed
SANDO Found sporadically w/T251I and P587L in a 80 yr. old male (Weiss and Saneto, 2010)
PubMed
Alpers Found in trans with W748S and E1143G in a 11 mo. old with epilepsy and encephalopathy (Isohanni et al., 2011)
PubMed
Liver Diseases Found in trans w/A467T in a 2 y.o. pt. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A467T in an 8 y.o. pt. with seizures, muscle weakness, hypotonia, ataxia, hearing loss, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A467T in a 1 y.o. with seizures, elevated transaminases, and increased signal basal ganglia Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ W748S in a 5 y.o. pt. w/myclonic seizures, liver failure, and hypotonia Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ W748S in a 7 y.o. w/ seizures and cortical blindness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ W748S in a 3 y.o. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ W748S in a 6 y.o. pt. with GI issues and irregular occipital lobe. Sibling died from VPA induced organ failure. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found as a homozygote in a 2 month old with seizures, an abnormal MRI, and abnormal respiratory enzymes. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Encephalopathy Found in trans w/ R1096C in a 2 y.o. w/ hypotonia, ptosis, hepatic failure, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Failure to thrive Found in trans w/ P1073L in a 2 y.o. w/ hypotonia, and gastro-esophageal reflux. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in trans w/ T25IL and P587L in an 80 y.o. w/ ptosis, PEO, peripheral neuropathy, and abnormal muscle histology. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A143V in a 4 y.o. w/ hypotonia, encephalopathy, seizures, hepatic failure, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A143V in a 38 y.o. w/ ataxia, peripheral neuropathy, hearing loss, and seizures Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in trans w/ c.3104+3a→t in a 63 y.o. w/ PEO, ptosis, hearing loss, muscle weakness and ragged red fibers Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A143V in an 8 y.o. w/ seizures and an abnormal MRI Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ A143V in a 37 y.o. symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Alpers Found in trans w/W748S in a 6 yr. 4 mo. with micro-vesicular fatty changes of the liver, myclonic seizures, and ataxia (Hunter et al., 2011)
PubMed
Alpers found in trans w/W7484S in a 6 yr. 9 mo. with seizures, developmentally delayed, and ataxia. (Hunter et al., 2011)
PubMed
Alpers Found in trans w/A467T in a 3 y.o. w/seizures, developmentally delayed, and ataxia (Hunter et al., 2011)
PubMed
Alpers Found in trans w/A467T in a 11 mo. old w/seizures and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/ A467T in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Alpers Found in trans w/A467T in a 10 mo. old female with seizures and brain stem dysfunction. History revealed that a 24 y.o. cousin died from Alpers whom harbored a homozygous A467T variant. (McCoy et al., 2011)
PubMed
Alpers and Leigh's encephalopathy Found in trans w/A467T in a 3.5 mo. old female with seizures and Alpers. Post mortem studies revealed Leigh's encephalopathy (Scalais et al., 2012)
PubMed
Optic atrophy Also found in w/ c.3104+3A>T in a 63 y.o. male with exercise intolerance, hearing loss, ptosis, and parkinsonism. (Milone et al., 2011)
PubMed
Parkinsonism Found in trans w/S1104C in a 59 y.o. male with mtDNA deletions and cerebellar ataxia (Lax et al., 2012b)
PubMed
PEO Found in trans w/G746S in a 36 y.o. male with PEO, peripheral neuropathy, and ataxia (Lax et al., 2012a)
PubMed
PEO Found in compound with T251I in a 45 yo female with mtDNA deletions Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Encephalopathy Found as a heterozygous mutation with A467T in a patient with epilepsy (Tzoulis et al., 2013)
PubMed
Encephalopathy Found w/A467T in a 6 mo. child w/epilepsy and death at 6 mo. (Tzoulis et al., 2014)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/T251I andP587L with PEO, muscle weakness, and cognitive impairment. Similar to SANDO, but no dysarthria. (Bereau et al., 2016)
PubMed
SANDO Found in trans w/A467T with ataxia, sensory neuropathy, dysarthria, and PEO. (Bereau et al., 2016)
PubMed
Gait disturbance Found w/R627Q in a 29 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
mild ophthalmoparesis Found in trans with R627Q in a 33 y.o. male with sensory ataxia and neuroathy (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: T849X
cDNA Position: 2544 (insertion of c with fs868X) (exon 16)
Disease Genetics Frequency Reference
Alpers Found in trans with A467T and in cis with Q1236H (Wong et al., 2008)
PubMed
Amino Acid Substitution: T851A
cDNA Position: 2551 a→g (exon 16)
Disease Genetics Frequency Reference
Alpers Found in trans w/R1047W. Not found in over 100 control alleles (Wiltshire et al., 2008)
PubMed
Alpers Found in trans w/H277L. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Opthmalplegia and seizures Found in trans w/P163S in a 21 y.o. female with peripheral neuropathy, seizures, dysarthria and bilateral ptosis 2 in 322 mitochondrial disease patients (Woodbridge et al., 2012)
PubMed
Opthmalplegia and peripheral neuropathy Found in trans w/N468D in a 49 y.o. female with ptosis, lower limb weakness, sensory ataxia, gastrointestinal symptoms, and peripheral neuropathy 2 in 322 mitochondrial disease patients (Woodbridge et al., 2012)
PubMed
Amino Acid Substitution: R852C
cDNA Position: 2554 c→t (exon 16)
Disease Genetics Frequency Reference
Alpers Compound with A467T Not found in 300 control chromosomes (Nguyen et al., 2006)
PubMed
Ataxia Neuropathy Found in trans w/ G11D-R627Q (Wong et al., 2008)
PubMed
Alpers Found in cis w/G11D and in trans w/W748S, and in a 2nd pt. found in cis w/G11D and in trans w/A467T. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Alpers Found in cis w/G11D and in trans w/ A467T. In a 2nd pt., found in cis w/G11D and in trans w/ W748S and E1143G. (Stewart et al., 2009)
PubMed
Leigh Syndrome Found in cis with G11D and in trans with W748S (Naess, et al., 2009)
PubMed
Multiple system atrophy Found with G11D in a 58 y.o. female with progressive cerebellar atrophy. Pt. had mtDNA deletions and mtDNA depletion. (Mehta et al., 2011)
PubMed
Seizures and liver failure Found in trans w/ A467T and in cis w/ G11D in a 8 mo. w/ seizures, liver failure, and lactic acidosis. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Encephalopathy Found in cis w/ G11D and in trans w/ R627Q in a 25 y.o. w/ dementia, encephalopathy, and stroke. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Alpers Found in trans w/A467T in a 5 y.o. w/seizures, ataxia, and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/A467T in a 21 mo. old female with blindness, anarthria, hypotonia, and epilepsy (McCoy et al., 2011)
PubMed
Alpers and PEO Found in trans with W748S in a pediatric female patient with hypotonia, developmental delay, ataxia, and seizures (Vasta et al., 2012)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in cis w/P587L and T251I in a 50 y.o. with PEO, muscle weakness, and polyneuropathy. Similar to SANDO, but no dysarthria. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: R852H
cDNA Position: 2555 g→a (exon 16)
Disease Genetics Frequency Reference
Alpers Found in trans w/ W748S in a 3 y.o. w/ Alpers Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: R853W
cDNA Position: 2557 c→t (exon 16)
Disease Genetics Frequency Reference
PEO with ptosis Found as compound in trans with P587L Parkinsonism in compound in trans with G737R 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez - Vioque et al., 2006)
PubMed
Parkinsonism (Davidzon et al., 2006)
PubMed
Parkinsonism Found in trans with G737R in a 32 y.o. female with early signs of Parkinsonism and COX negative muscle fibers. Levodopa-responsive. (Rempe et al., 2016)
PubMed
Amino Acid Substitution: R853Q
cDNA Position: 2558 g→a (exon 16)
Disease Genetics Frequency Reference
Myocerebrohepatopathy In trans with T251I-P587L (Wong et al., 2008)
PubMed
Amino Acid Substitution: V855L
cDNA Position: 2563 g→t (exon 16)
Disease Genetics Frequency Reference
Seizures Found in trans w/ G737R in an 8 mo. w/ seizures, liver failure, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: V855A
cDNA Position: 2564 t→c (exon 16)
Disease Genetics Frequency Reference
Heterozygous with muscle weakness. (Wong et al., 2008)
PubMed
Amino Acid Substitution: A862T
cDNA Position: 2584 g→a (exon 16)
Disease Genetics Frequency Reference
Ataxia Neuropathy Compound heterozygous with R964C (Wong et al., 2008)
PubMed
PEO with ataxia Found in trans w/R1047W in a 61 y.o. with PEO, ataxia, and mtDNA deletions (Stewart et al., 2009)
PubMed
Cerebellar ataxia, neuropathy, epilepsy, and restless leg syndrome Found heterozygous with R964C in 2 siblings that died in their early 20's (Stricker et al., 2009)
PubMed
Alpers-like Found in trans with R1081Q in a 7 y.o. male with Alpers-like symptoms. Affected sibling. (Ferreira et al., 2011)
PubMed
Alpers-like Found in trans with R1081Q in a 4 y.o. male with Alpers-like symptoms. Affected sibling. (Ferreira et al., 2011)
PubMed
Myelopathy,myopathy, peripheral neuropathy and subcortical grey matter degeneration Found in trans w/H277L in a 66 y.o. female with mtDNA deletions and subcortical grey matter degeneration (McKelvie et al., 2012)
PubMed
PEO Found in trans w/ R1047W in a 61 y.o. female with PEO, ptosis, peripheral neuropathy, ataxia, and dysarthria. (Lax et al., 2012a)
PubMed
Amino Acid Substitution: N864S
cDNA Position: 2591 a→g (exon 16)
Disease Genetics Frequency Reference
PEO Found as compound with T251I-P587L Not found in 280 control chromosomes (Van Goethem et al., 2003c)
PubMed
Amino Acid Substitution: IVS16-10 c>t
cDNA Position: IVS16-10 c>t (exon 16)
Disease Genetics Frequency Reference
Cerebellar ataxia, sensory neuropathy, and dysphagia Homozygous. Found in a 60 yr. old patient (Schulte et al., 2009)
PubMed
Amino Acid Substitution: R869Q
cDNA Position: 2606 g→a (exon 17)
Disease Genetics Frequency Reference
Myopathy w/ neurogenic atrophy; sensomotor axonal polyneuropathy, ataxia, and ptosis Autosomal recessive, found in a 32 yr. old pt. <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
PEO Found in trans w/ K319E in a 44 y.o. w/ PEO, ataxia, neuropathy, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
SANDO Found in trans w/P587L and w/T251I in a 34 y.o. female with ataxia, ptosis, diabetes and mtDNA deletions. (Hanisch et al., 2014)
PubMed
Amino Acid Substitution: E873X
cDNA Position: 2617 g→t (exon 17)
Disease Genetics Frequency Reference
Alpers Found in trans with A467T and under goes nonsense-mediated decay for mono-allelic expression of POLG Not found in 40 alleles from non-Alpers mitochondrial disease patients (Chan et al., 2005b)
PubMed
Alpers Found in trans with A467T Not found in 40 alleles from non-Alpers mitochondrial disease patients (Naviaux and Nguyen, 2004)
PubMed
Alpers Found in trans w/A467 in and 18 mo. old male w/ mtDNA depletion (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Amino Acid Substitution: Q879H
cDNA Position: 2637 g→t (exon 17)
Disease Genetics Frequency Reference
Liver failure and encephalopathy Found in cis with E1143G and in trans with A467T-T885S Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Alpers w/ valproate-induced hepatic failure Found in cis with E1143G and in trans with A467T-T885S in a 2 y.o. male (McFarland et al., 2009)
PubMed
Amino Acid Substitution: T885S
cDNA Position: 2653 a→t (exon 17)
Disease Genetics Frequency Reference
Alpers Found in cis with A467T and in trans with Q879H-E1143G Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Alpers w/ valproate-induced hepatic failure Found in cis with A467T, and in trans w/Q879H and E1143G (McFarland et al., 2008)
PubMed
Amino Acid Substitution: L886P
cDNA Position: 2657 t→c (exon 17)
Disease Genetics Frequency Reference
Alpers Found in trans w/ A467T (Wong et al., 2008)
PubMed
Amino Acid Substitution: G888S
cDNA Position: 2662 g→a (exon 17)
Disease Genetics Frequency Reference
Alpers Compound heterozygous with L83P in 10 yr. old (Bao et al., 2007) (Wong et al., 2008)
PubMed
Amino Acid Substitution: G888D
cDNA Position: 2663 g→a (exon 17)
Disease Genetics Frequency Reference
Seizures and liver failure Found in trans w/ W748S in a 2 y.o. w/ seizures, hepatic failure, ketosis and abnormal MRI Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Alpers Found in trans w/L304R in a patient showing psychomotor retardation, epileptic encephalopathy, progressive cerebral atrophy, and altered liver enzymes. 1 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome (Navarro-Sastre et al., 2012)
PubMed
Amino Acid Substitution: A889T
cDNA Position: 2665 g→a (exon 17)
Disease Genetics Frequency Reference
PEO Sporadic / unknown Compound with R579W Compound with E1143G Filosto, 2003: not detected in 120 healthy control alleles (Filosto et al., 2003)
PubMed
PEO Sporadic / unknown Compound with R579W Compound with E1143G (Hisama et al., 2005)
PubMed
Amino Acid Substitution: D890A
cDNA Position: 2669 a→c (exon 17)
Disease Genetics Frequency Reference
MNGIE-like Found as a heterozygous mutation in a 20 y.o. male w/ progressive gastrointestinal dysmotility, cachexia, PEO, and peripheral neuropathy. (Parsun and Koeberl, 2014)
PubMed
Amino Acid Substitution: D892GfsX39
cDNA Position: 2675 ins g (exon 17)
Disease Genetics Frequency Reference
Found in trans w/ W748S in a 9 mo. old pt. with a deceased sibling. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: E895G
cDNA Position: 2684 a→g (exon 17)
Disease Genetics Frequency Reference
Myopathic MDS Found in one newborn with floppiness and 20% liver mtDNA depletion, heterozygous (Spinazzola et al., 2009)
PubMed
Amino Acid Substitution: T914A
cDNA Position: 2740 a→g (exon 18)
Disease Genetics Frequency Reference
Multiple Sclerosis-like illness Found as a heterozygous mutation w/Y452C in a 56 yr. old. Pt. first diagnosed w/ optic neuritis and MS 19 yrs. earlier. Currently has ragged-red muscle fibers, ptosis, myopathies, and mtDNA deletions. (Echaniz-Laguana et al., 2010)
PubMed
Alpers Found in trans with A467T in a 9 mo. old with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Amino Acid Substitution: T914P
cDNA Position: 2740 a→c (exon 18)
Disease Genetics Frequency Reference
Alpers Found in trans with A467T. Not found in 300 control chromosomes (Nguyen et al., 2006) 
PubMed
Encephalopathy Found in trans with A467T in an 8 y.o. male w/encephalopathy and myoclonus . Not found in 250 control individuals (Horvath et al., 2006) 
PubMed
Alpers Found in trans with A467T in a 7 mo. female w/ Alpers Not found in 300 healthy French control chromosomes (Naimi et al., 2006)
PubMed
Alpers Found in trans w/ A467T (Wong et al., 2008)
PubMed
adPEO Heterozygous, Ptosis, exercise intolerance, fatigue, ragged red fibers (Wong et al., 2008)
PubMed
Alpers Found in trans w/R1096C, and in a 2nd pt. found in trans w/R627W. Also found in trans w/A467T in 2 other pts. Found in 2 additional pts. in trans w/W748S. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Alpers In trans w/ A467T (Taanman et al., 2008)
PubMed
Epilepsy, myoclonic, and developmental delay ar, Found as a compound heterozygous mutation w/ A467T <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Epilepsy Found heterozygous with A467T in a 10 mo. old male with myoclonic seizures and jerks, and developmental regression. (Dhamija et al., 2011)
PubMed
Alpers Found in trans with E1143G and W748S in a 2.5 y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Seizures Found in trans w/ A467T in a 3 y.o. w/ seizures, hypotonia, encephalopathy, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ W748S in a 5 y.o. w/ seizures Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A467T in a 5 y.o. w/ seizures, hearing loss, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ W748S in an 8 mo. w/ seizures, hypotonia, abnormal MRI, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A467T in a 9 mo. w/ seizures, hypotonia, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures and liver failure Found in trans w/ A467T in a 4 y.o. with liver failure, seizures, and failure to thrive Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A467T in an 8 mo. w/ seizures, respiratory failure, and an abnormal MRI Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
MSCAE Found in trans w/ W748S in a 15 y.o. female with mitochondrial spinocerebellar ataxia and epilepsy. (Hinnell et al., 2012)
PubMed
Alpers Found in compound with A467T in a 15 month female with mtDNA depletion Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Epilepsy Found in compound with W748S in a 6 yo male with epilepsy and hepatic cholestasis and cytolysis, and mtDNA deletions Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
PEO Found in compound with the intronic mutation C3104+3A>T in a 37 y.o. male with PEO. Myopathy, dysphagia, and muscle weakness developed by age 55. Pt.'s older brother was diagnosed with PEO at age 65, and pt.'s adult daughters are not affected. Pt. had COX negative muscle fibers and a splice variatant leading to a deletion of exon 19. (Roos et al., 2013)
PubMed
Amino Acid Substitution: W918R
cDNA Position: 2752 t→c(exon 18)
Disease Genetics Frequency Reference
PEO with Parkinsonism ar, Compound (in trans) heterozygous with M430L Absent in 200 control alleles (Invernizzi et al., 2008)
PubMed
PEO Found in trans with M430L in a 42 y.o. male with PEO and mtDNA (Ferreira et al., 2011)
PubMed
Amino Acid Substitution: M919T
cDNA Position: 2755 a→t (exon 18)
Disease Genetics Frequency Reference
PEO Found in compound w/A467T in a 23 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
SANDO Found in trans with Y986D in a 34 y.o. with PEO, ataxia, sensory neuropathy, dysarthria, depression, and migraines. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: G923D
cDNA Position: 2768 g→a (exon 18)
Disease Genetics Frequency Reference
PEO Found as a homozygous mutation in 2 patients w/ mtDNA deletions. Also found as a heterozygous mutation with little or no symptoms. Lamantea, 2002: absent in 100 control DNA samples (Lamantea et al., 2002)
PubMed
PEO ad PEO. Studied the pathological and biochemical consequences of several PEO mutations by modeling the amino acid changes and structure pol γ. In order to correlate mutation and disease severity. (Graziewicz et al., 2004)
PubMed
PEO Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci. (Stuart et al., 2006)
PubMed
Amino Acid Substitution: G923R
cDNA Position: 2767 c→g (exon 18)
Disease Genetics Frequency Reference
Reference # rs60636456
PubMed
Amino Acid Substitution: K925R fs42X
cDNA Position: 2772_2773 delG
Disease Genetics Frequency Reference
Prematurity, epilepsy, deafness, retinitis pigmentosa, hemiparesis, and liver failure Found in trans w/A467T. <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Amino Acid Substitution: D930N
cDNA Position: 2788 g→a (exon 18)
Disease Genetics Frequency Reference
Alpers Infantile Alpers w/ bilateral lesions of thalami. Hepatocerebral MDS patient, Found in trans w/ W748S. (Spinazzola et al., 2009)
PubMed
Amino Acid Substitution: H932Y
cDNA Position: 2794 c→t (exon 18)
Disease Genetics Frequency Reference
PEO and mtDNA deletions Found in compound w/T251I/ P587L in1 pt. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions. Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians (Di Fonzo et al., 2003)
PubMed
PEO Found in compound with G1051R in 2 family members PEO not seen in 120 control subjects. (Mancuso et al., 2004a)
PubMed
Isolated distal myopathy of the upper limbs w/ mtDNA depletion (Giordano et al., 2010)
PubMed
PEO Found in trans w/ P587L and T251I in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Peripheral Neuropathy Found in trans w/ T251I and P587L in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: S933R
cDNA Position: 2799 t→g (exon 18)
Disease Genetics Frequency Reference
PEO Found in trans w/ Q1214LX in a 60 y.o. w/ PEO, dementia, myopathy, and abnormal muscle histology Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ A957V in a 3 mo. w/ seizures, hypotonia, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: R943C
cDNA Position: 2827 c→t (exon 18)
Disease Genetics Frequency Reference
Myocerebrohepatopathy In cis w/ E1143G and in trans w/G737R (Wong et al., 2008)
PubMed
PEO and Parkinsonism Found in trans w/H227L in a 78 y.o. Japanese malewith parkinsonism. Also found as a heterozygous mutation in a second unrelated 68 y.o. malewith PEO. not found in 50 ethnically matched controls (Sato et al., 2011)
PubMed
Amino Acid Substitution: R943H
cDNA Position: 2828 g→a (exon 18)
Disease Genetics Frequency Reference
PEO ad PEO. Found in 2 siblings as a homozygous mutation Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians (Lamantea et al., 2002)
PubMed
PEO ad PEO. Studied the pathological and biochemical consequences of several PEO mutations by modeling the amino acid changes and structure pol γ. In order to correlate mutation and disease severity. (Graziewicz et al., 2004)
PubMed
PEO Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci. (Stuart et al., 2006)
PubMed
Premature ovarian failure Ad, and premature ovarian failure <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
PEO and Parkinsonism Found as a heterozygous mutation in a 63 y.o. male with PEO, resting tremors, dysarthria, and poly neuropathy, fatigue, hearing lass, and Parkinsonism (Brandon et al., 2013)
PubMed
Amino Acid Substitution: H945L
cDNA Position: 2834 a→t (exon 18)
Disease Genetics Frequency Reference
PEO and Parkinsonism Found as a heterozygous mutation in an 80 y.o. female with PEO, ptosis, neuropathy, cognitive decline, ragged red fibers, mtDNA deletions, and striatal dopamine deficiency. (Delgado-Alvarado et al., 2015)
PubMed
Amino Acid Substitution: K947R
cDNA Position: 2840 g→a (exon 18)
Disease Genetics Frequency Reference
PEO and ovarian failure Compound heterozygote found w/ expansion of a polyQ (18Q) stretch. (Baruffini et al., 2011)
PubMed
Amino Acid Substitution: Y951N
cDNA Position: 2851 t→a (exon 18)
Disease Genetics Frequency Reference
Peripheral Neuropathy Found as a heterozygous mutation in 22 y.o. w/ peripheral neuropathy Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
3-methyl glutaconic aciduria Found as a heterozygous mutation in a 23 y.o. female with progressive muscle weakness, cataracts, and ovarian dysgenesis (Bekheirnia et al., 2012)
PubMed
Amino Acid Substitution: R953C
cDNA Position: 2857 c→t (exon 18)
Disease Genetics Frequency Reference
PEO ad Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes. (Luoma et al., 2004)
PubMed
Reference # rs11546842
PubMed
PEO Found in trans w/ W748S in a 51 y.o. w/ peripheral neuropathy, ptosis, hypotonia, ataxia, and seizures. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Autosomal recessive PEO, found as a homozygous mutation in 3 affected siblings and heterozygous in 2 asymptomatic siblings from the same family. One unaffected sibling had no POLG mutations. Symptoms started in early 20's of the 3 affected siblings which include abnormal gait, parkinsonism, sensory neuropathy, cardiomyopathy, and depression. (Gurgel-Giannetti et al., 2012)
PubMed
MNGIE-like Found in compound with W748S in a 50y.o. male with cognitive impairment, muscle weakness, diarrhea, vomiting, ptosis, and opthalmoparesis. (Tang et al., 2012)
PubMed
MItochondrial toxicity Found as a heterozygous mutation in a HIV positive patient with mitochondrial toxicity (Li et al., 2016)
PubMed
Amino Acid Substitution: Y955C
cDNA Position: 2864 a→g (exon 18)
Disease Genetics Frequency Reference
PEO ad PEO in a family w/ mtDNA deletions absent in 432 control chromosomes (Van Goethem et al., 2001)
PubMed
PEO Found as a heterozygous mutation in 3 Belgian families w/ PEO Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians  (Lamantea et al., 2002)
PubMed
PEO ad PEO. Studied the pathological and biochemical consequences of several PEO mutations by modeling the amino acid changes and structure pol γ. In order to correlate mutation and disease severity. (Graziewicz et al., 2004)
PubMed
Parkinsonism Premature ovarian failure Alzheimer's disease Most severe autosomal dominant mutation in POLG, drastically lowers polymerase catalysis, promotes stalling and errors in replication. Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes. ( Luoma et al., 2004)
PubMed
PEO and Premature ovarian failure Found as a heterozygous and homozygous mutation in 3 generations of women in the same family with Premature ovarian failure and PEO. Also found in trans w/Q1236H. (Pagnamenta et al., 2006)
PubMed
PEO Studied recombinant protein and found that the Y955C POLG enzyme cause error-prone DNA synthesis (Ponamarev et al., 2002)
PubMed
PEO Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci. (Stuart et al., 2006)
PubMed
PEO Studied the yeast homologue that had mtDNA depletion and deletions with altered dNTP pools (Baruffini et al., 2006)
PubMed
PEO Studied 4 pts. with adPEO and that were heterozygous for Y955C which revealed a low instance of mtDNA point mutations. (Kollberg et al., 2005)
PubMed
PEO Y955C POLG was targeted transgenically to the murine heart. The mice had cardiomyopathy and mtDNA depletion. (Lewis et al., 2007)
PubMed
PEO/Alzheimer's Myopathy, COX deficient muscle fibers, and mtDNA depletion found in 2 siblings who developed Alzheimer's and thought to have aged prematurely. (Melberg et al., 2005)
PubMed
Found as a heterozygous mutation w/ hearing loss, failure to thrive, generalized ETC complex deficiency (Wong et al., 2008)
PubMed
PEO Found in cis w/ G517V in a 47 y.o. w/ PEO, ptosis, myopathy, and neuropathy Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found as a heterozygous mutation in a 45 y.o. w/ myopathy and PEO Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in a Chinese population with Parkinsonism at an allelic frequency of 0.816 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
PEO and Parkinsonism Found as heterozygous mutations in siblings in Japan (Mukai et al., 2013)
PubMed
PEO and infertility Found as a heterozygous dominate mutation in a patient with PEO and ovarian failure with mtDNA deletions,and COX negative muscle fibers (Siibak et al., 2017)
PubMed
Ptosis and ophthalmoparesis Found as a heterozygous mutation in a 45 y.o. female with ataxia (Vogel et al., 2017)
PubMed
Ptosis and ophthalmoparesis Found as a heterozygous mutation in a 29 y.o. male with a speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
Ptosis and ophthalmoparesis Found as a heterozygous mutation in a 26 y.o. male with a speech abnormalities, and swallowing abnormalities (Vogel et al., 2017)
PubMed
PEO and Parkinsonism Found as a heterozygous mutation in a 59 y.o. female with parkinsonism, diabetes, hearing loss, and cortical atrophy. Patient was positive for mtDNA deletions. (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: Y955H
cDNA Position: 2864 a→t (exon 18)
Disease Genetics Frequency Reference
Progressive multi-systemic disorder Found in cis w/Q1236H in an 8 month old with weight loss, hearing loss, myopathy, liver failure, decreased ATP production, COX negative muscle fibers, and ragged red fibers. (Siibak et al., 2017)
PubMed
Amino Acid Substitution: A957S
cDNA Position: 2869 g→t (exon 18)
Disease Genetics Frequency Reference
PEO Found as both a heterozygous and as a homozygous mutation in one individual in two Sicilian families. Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians (Lamantea et al., 2002)
PubMed
PEO ad PEO. Studied the pathological and biochemical consequences of several PEO mutations by modeling the amino acid changes and structure pol γ. In order to correlate mutation and disease severity. (Graziewicz et al., 2004)
PubMed
PEO Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci. (Stuart et al., 2006)
PubMed
Amino Acid Substitution: A957P
cDNA Position: 2869 g→c (exon 18)
Disease Genetics Frequency Reference
Alpers Found in compound w/A467T in a 8 mo. old male w/ multiple complex deficiencies de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder (de Vries et al., 2007)
PubMed
Alpers Found in compound w/A467T in a 6 mo. old w/ infantile hepatocereberal syndrome. Ferrari, 2005: absent in 200 consecutive control individuals from Northern continental Europe as well as 350 Italian controls (Ferrari et al., 2005)
PubMed
Epilepsy, liver failure, occipital strokes, and growth retardation ar, found as a compound heterozygous mutation w/ A467T <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Amino Acid Substitution: A957V
cDNA Position: 2870 c→t (exon 18)
Disease Genetics Frequency Reference
Seizures Found in trans w/ C1077G in a 2 y.o. w/ seizures, encephalopathy, and hypotonia Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Found in trans w/ G737R in a 4 mo. Symptoms not noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found in trans w/ S933R in a 3 mo. w/ seizures, hypotonia, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Myocerebrohepatopathy spectrum disorder Found in compound w/ I1185T in an 8 mo. Japanese female. Hypotonia, failure to thrive, hepatomegaly, and developmental regression. Hetero compound not found in 1000 Genome Project, ESP6500 data base, nor HGVD (Montassir, et al., 2014)
PubMed
Amino Acid Substitution: F961S
cDNA Position: 2882 t → c (exon 18)
Disease Genetics Frequency Reference
PEO ad PEO (Adachi et al., 2002)
PubMed
Amino Acid Substitution: A962T
cDNA Position: 2884 g→a (exon 18)
Disease Genetics Frequency Reference
Ataxia Found in trans w/ R964C in a 14 y.o. w/ ataxia, muscle weakness, and central hypoventilation Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: R964C
cDNA Position: 2890 c → t (exon 18)
Disease Genetics Frequency Reference
Mitochondrial toxicity susceptibility to NRTIs Found in a HIV1 patient with hyperlactatemia following 1 yr. of d4T and 3TC anti-viral treatment Not found in 26 Thai HIV-1-infected individuals, or 110 healthy volunteers (Yamanaka et al., 2007)
PubMed
Ataxia Neuropathy Found in trans w/ A862T, and found as a heterozygous mutation w/ ataxia and hypotonia (Wong et al., 2008)
PubMed
Cerebellar ataxia, neuropathy, epilepsy, and restless leg syndrome Found heterozygous with A862T in 2 siblings that died in their early 20’s (Stricker et al., 2009)
PubMed
Ataxia Found in trans w/ A962T in a 14 y.o. w/ ataxia, muscle weakness, and central hypoventilation Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
PEO Found in trans w/Q53-Q55 duplicate in an 8 y.o. male with recessive ataxia, PEO, and hyoptonia Ohba et al., 2013
PubMed
Amino Acid Substitution: L965X
cDNA Position: 2894 t→g (exon 18)
Disease Genetics Frequency Reference
Myoclonus epilepsy ar, found in cis with E1143G and in trans with R627Q-Q1236H w/ liver dysfunction and encephalopathy Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Amino Acid Substitution: L966R
cDNA Position: 2897 t→g (exon 18)
Disease Genetics Frequency Reference
Alpers Compound with A467T Not found in 300 control chromosomes (Nguyen et al., 2006)
PubMed
Alpers In trans w/A467T. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Alpers Found in trans w/A467T in a 1 y.o. w/ seizures and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/A467T in a 1 y.o. w/ seizures and developmentally delayed (Hunter et al., 2011)
PubMed
Alpers Found in trans w/A467T in a 17 mo. old male with seizures and encephalopathy (McCoy et al., 2011)
PubMed
Amino Acid Substitution: G975stop
cDNA Position: 2923 c→t (exon 18)
Disease Genetics Frequency Reference
Seizures Found as a heterozygous mutation in a 6 yo female with dystonia, psychomotor delay, and seizures Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Amino Acid Substitution: Y986D
cDNA Position: 2956 t→g (exon 18)
Disease Genetics Frequency Reference
SANDO Found in trans with M919T in a 34 y.o. with PEO, ataxia, sensory neuropathy, dysarthria, depression, and migraines. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: T989dup(CAA/)
cDNA Position: 2963_2975 ins CAA (exon 18)
Disease Genetics Frequency Reference
PEO Found in trans with T251I and P587L in a 36 y.o. female with cornieal edema and muscle weakness. One brother affected and has both variants and one unaffected sister with no mutations. Not found in 100 random controls (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: S998W
cDNA Position: 2993 c→g (exon 19)
Disease Genetics Frequency Reference
Reference # rs79840247
PubMed
Amino Acid Substitution: S998L
cDNA Position: 2993 c→t (exon 19)
Disease Genetics Frequency Reference
PEO Found as a compound heterozygote with D1184H in a 64 y.o. female with PEO, bilateral ptosis, and encephalopathy. (Martikainen et al.,)
PubMed
Amino Acid Substitution: W1020X
cDNA Position: 3057 g→a (exon 19)
Disease Genetics Frequency Reference
Alpers Compound with A467T (Nguyen et al., 2005)
PubMed
Amino Acid Substitution: Q1024X
cDNA Position: 3067 c→t (exon 20)
Disease Genetics Frequency Reference
Seizures Found in trans w/ A467T in a 2 y.o. w/seizures, hearing loss, and hemiparesis Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: c. 3104 +3a→t
cDNA Position: 3104 +3a→t (splice variant between ex. 19 and 20)
Disease Genetics Frequency Reference
PEO Found in trans w/ F749S in a 66 y.o. w/ PEO, ptosis, myopathy, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Optic atrophy Found in trans w/F749S in a 65 y.o. male with ptosis, dysphagia, exercise induced myalgia, limb weakness, and diabetes. Also found in trans w/ G8484S in a63 y.o. male with exercise intolerance, hearing loss, ptosis, and parkinsonism. (Milone et al., 2011)
PubMed
PEO Found in trans w/ G848S in a 63 y.o. w/ PEO, ptosis, hearing loss, muscle weakness and ragged red fibers Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: c. 3104 +3a→t
cDNA Position: 3104 +3a→t (splice variant resulting in a deletion on exon 19)
Disease Genetics Frequency Reference
PEO Found in compound with the intronic mutation T914P in a 37 y.o. male with PEO. Myopathy, dysphagia, and muscle weakness developed by age 55. Pt.'s older brother was diagnosed with PEO at age 65, and pt.'s adult daughters are not affected. Pt. had COX negative muscle fibers and a splice variatant leading to a deletion of exon 19. (Roos et al., 2013)
PubMed
Amino Acid Substitution: V1044A
cDNA Position: 3131 t→c (exon 20)
Disease Genetics Frequency Reference
Alpers Found in trans with R722H in a 2.5 y.o. old with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Amino Acid Substitution: R1047Q
cDNA Position: 3140 g→a (exon 20)
Disease Genetics Frequency Reference
PEO Sporadic / unknown Not found in 250 control individuals (Agostino et al., 2003)
PubMed
Amino Acid Substitution: R1047W
cDNA Position: 3139 c→t (exon 20)
Disease Genetics Frequency Reference
Alpers Compound in trans with T851A Not found in over 200 control alleles (Wiltshire et al., 2008)
PubMed
PEO Found in trans w/A862T in a 61 y.o. with PEO, ataxia, and mtDNA deletions (Stewart et al., 2009)
PubMed
PEO Found in trans w/ A862T in a 61 y.o. female with PEO, ptosis, peripheral neuropathy, ataxia, and dysarthria. (Lax et al., 2012a)
PubMed
Amino Acid Substitution: K1050fsX44
cDNA Position: 3149 del a (exon 20)
Disease Genetics Frequency Reference
Seizures Found in trans w/ A467T in a 4 y.o. w/ seizures, ataxia, hypotonia, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: G1051R
cDNA Position: 3151 g→c (exon 20)
Disease Genetics Frequency Reference
PEO, SANDO ar Found as compound with H932Y not seen in 120 control subjects. (Mancuso et al., 2004a)
PubMed
Epilepsy ataxia and developmental delay Found in trans with R309H in a 32 y.o. male with severe neuropathy, achalasia, epilepsy, and developmentally delayed. (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: M1057T
cDNA Position: 3170 t→g (exon 20)
Disease Genetics Frequency Reference
PEO Found in trans w/F1164I in a71 y.o. with Ophthalmoparesis, ptosis, depression, and muscle weakness. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: P1073L
cDNA Position: 3218 c→t (exon 20)
Disease Genetics Frequency Reference
Hepatocerebral - Alpers symptoms Found in trans w/A467T in 2 pt., in trans w/ W748S in 1 pt., and in trans with G848S in 1 pt. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility. (Kurt et al., 2010)
PubMed
Alpers Found as a compound heterozygote w/ S305R in a 9 mo. pt. w/ Alpers (Baruffini et al., 2011)
PubMed
Failure to thrive Found in trans w/ G848S in a 2 y.o. w/ hypotonia, and gastro-esophageal reflux. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Myopathy Found as a heterozygous mutation in a 5 yo female with epilepsy, myopathy, and tubulopathy Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Amino Acid Substitution: G1076V
cDNA Position: 3227 g→t (exon 20)
Disease Genetics Frequency Reference
PEO Sporadic / unknown Not detected in 120 healthy control alleles (Filosto et al., 2003)
PubMed
Amino Acid Substitution: C1077G
cDNA Position: 3229 t →g (exon 20)
Disease Genetics Frequency Reference
Seizures Found in trans w/ A957V in a 2 y.o. w/ seizures, encephalopathy, and hypotonia Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: I1079L
cDNA Position: 3235 a→c (exon 20)
Disease Genetics Frequency Reference
adPEO Heterozygous Hearing loss, and ptosis (Wong et al., 2008)
PubMed
Amino Acid Substitution: S1080T
cDNA Position: 3239 g→c (exon 20)
Disease Genetics Frequency Reference
Intracranial calcifications Found as a heterozygous mutation in a 55 y.o. female with action tremors, peripheral neuropathy, hearing loss, and intracranial calcifications (Sidirooulos et al., 2013)
PubMed
Amino Acid Substitution: S1080I
cDNA Position: 3239 g→t (exon 20)
Disease Genetics Frequency Reference
Epilepsy Found in compound with L79F in an 8 yo female with adrenocortical insufficiency and hypothyroidy Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Epilepsy Found in compound with L79F in an 8 yo female with epilepsy, cerebellar ataxia, and ptosis Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Amino Acid Substitution: R1081dup
cDNA Position: 3240– 3242 ins ccg (R) (exon 20)
Disease Genetics Frequency Reference
Alpers Found in cis w/ L392V and in trans w/L304R (Cardenas et al., 2010)
PubMed
Seizures Found in trans w/ L304R in a 1 y.o. w/ seizures and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: R1081Q
cDNA Position: 3241 c→g (exon 20)
Disease Genetics Frequency Reference
Alpers-like Found in trans with A862T in a 7 y.o. male with Alpers-like symptoms. (Ferreira et al., 2011)
PubMed
Alpers-like Found in trans with A862T in a 4 y.o. male with Alpers-like symptoms. Affected sibling (Ferreira et al., 2011)
PubMed
Cerebellar ataxia Found as a heterozygote in a 29 y.o. female with cerebellar ataxia and diabetes (Ferreira et al., 2011)
PubMed
Amino Acid Substitution: R1081P
cDNA Position: 3242 g→c (exon 21)
Disease Genetics Frequency Reference
PEO Found in trans w/ L304R in a 10 y.o. w/ ataxia, seizures, PEO, and dystonia Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: F1092L
cDNA Position: 3276 t→g (exon 21)
Disease Genetics Frequency Reference
Reference # rs74034411
PubMed
Amino Acid Substitution: S1095R
cDNA Position: 3285 c→g (exon 21)
Disease Genetics Frequency Reference
adPEO Hearing loss, ptosis, Muscle weakness, optic atrophy (Wong et al., 2008)
PubMed
Amino Acid Substitution: S1095R
cDNA Position: 3286 c→g (exon 21)
Disease Genetics Frequency Reference
Failure to thrive ar, found in trans w/ D1184N. Aslo, impaired liver functions, deafness, and demyelating sensomotor neuropathy <0.5% of Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Hepatic failure Found in trans w/ A467T in a 6 mo. w/ hypotonia, liver failure, abnormal muscle histology, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Myocerebrohepatopathy Found w/A467T in a 4 y.o. boy with hypotonia, failure to thrive, and abnormalities in cranial nerve enhancement (Horst et al., 2014)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in cis w/T251I and P587L with PEO, muscle weakness, ataxia, and polyneuropathy. Similar to SANDO, but no dysarthria. (Bereau et al., 2016)
PubMed
SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) Found in trans w/T251I and P587L with ataxia, sensory neruopathy, PEO, deafness, and dysphagia. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: R1096C
cDNA Position: 3286 c→t (exon 21)
Disease Genetics Frequency Reference
PEO Sporadic or ar in PEO Agostino 2003: Not found in 250 individuals (Agostino et al., 2003)
PubMed
Alpers Found in trans with P648R in PEO-myopathy. Found as homozygous mutation with Q1236H in Alpers Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Alpers Found as compound w/ Q1236H . (Wong et al., 2008)
PubMed
Alpers Found in trans w/T914P, and homozygous in a 2nd pt. (Ashley et al., 2008) and a correction in (Ashley et al., 2009)
PubMed
Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Found with R627Q in a 43 yr. old patient (Schulte et al., 2009)
PubMed
Seizures Found as a homozygote in an 8 mo. old pt. with encephalopathy and seizures. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found as a homozygote in a 1 y.o. with seizures and liver failure. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Encephalopathy Found in trans w/ G848S in a 2 y.o. w/ hypotonia, ptosis, hepatic failure, and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Seizures Found as a homozygote in a 2 y.o. w/ seizures, lactic acidosis and developmentally delayed. Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
SANDO Found in trans w/L591F in a 48 y.o. female with SANDO and dysphagia. (Kurt et al. 2012)
PubMed
PEO Found in trans w/ W748S in a 49 y.o. male with PEO, ptosis, epilepsy and peripheral neuropathy (Lax et al., 2012a)
PubMed
PEO Found in trans w/A467T in a 42 y.o. male with PEO, ptosis and sensory neuropathy (Lax et al., 2012a)
PubMed
Amino Acid Substitution: R1096H
cDNA Position: 3287 g→a (exon 21)
Disease Genetics Frequency Reference
Alpers Found as a compound in trans with R627Q Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Alpers Found as a homozygous mutation in an 8 month old boy with liver failure and encephalopathy. (Bijarnia-Mahayet al., 2014)
PubMed
Amino Acid Substitution: N1098K
cDNA Position: 3294 t→g (exon 21)
Disease Genetics Frequency Reference
Alpers Found as a heterozygous mutation in a 6 y.o. female with epilepsy following myoclonic seizures. After 3 years of treatment the patient had major cognitive deterioration and loss of voluntary movement. Family members did not harbor N1098K POLG mutation. (Iodice et al., 2016)
PubMed
Amino Acid Substitution: S1104C
cDNA Position: 3311 c→g (exon 21)
Disease Genetics Frequency Reference
PEO Sporadic / unknown Found as compound with A467T Not found in 250 individuals (Agostino et al., 2003)
PubMed
Parkinsonism Found in trans w/G848S in a 59 y.o. male with mtDNA deletions and cerebellar ataxia (Lax et al., 2012b)
PubMed
Amino Acid Substitution: S1104F
cDNA Position: 3311 c→t (exon 21)
Disease Genetics Frequency Reference
Epilepsy Found with A467T in a 5 y.o. male. Patient also had myopathy and ataxia. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. (Sitarz et al., 2014)
PubMed
Amino Acid Substitution: A1105T
cDNA Position: 3313 g→a (exon 21)
Disease Genetics Frequency Reference
PEO Found as a heterozygous mutation and as a compound heterozygous mutation w/ N468D in 3 patients of the same family all w/PEO Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes. (Luoma et al., 2004)
PubMed
PEO Found d as a compound heterozygous mutation w/ N468D in 3 patients w/ mtDNA deletions and mutations. Proposed replication stalling as the principal cause of deletion formation. (Wanrooij et al., 2004)
PubMed
Amino Acid Substitution: V1106I
cDNA Position: 3316 g→a (exon 21)
Disease Genetics Frequency Reference
PEO ar, found in trans with T251I-P587L Not found in 500 Italian controls. (Horvath et al., 2006)
PubMed
Amino Acid Substitution: H1110Y
cDNA Position: 3328 c→t (exon 21)
Disease Genetics Frequency Reference
infantile hepatocerebral mtDNA depletion Heterozygous, found in cis Q1236H, & in trans w/ W748S+ E1143G (Taanman et al., 2008)
PubMed
Amino Acid Substitution: L1113P
cDNA Position: 3338 t→c (exon 21)
Disease Genetics Frequency Reference
Seizures Found in trans w/ A467T in a 1 y.o. with encephalopathy, seizures, and hepatic failure Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: R1128H
cDNA Position: 3383g→a (exon 21)
Disease Genetics Frequency Reference
Microcephaly Heterozygous, found w/ G517V (Wong et al., 2008)
PubMed
Amino Acid Substitution: H1134R
cDNA Position: 3401 a→g (exon 21)
Disease Genetics Frequency Reference
infantile hepatocerebral mtDNA depletion Heterozygous, found in trans with Y831C (Taanman et al., 2008)
PubMed
Amino Acid Substitution: E1136K
cDNA Position: 3406 g→a (exon 21)
Disease Genetics Frequency Reference
infantile hepatocerebral mtDNA depletion Heterozygous, found T251I+P587L (Taanman et al., 2008)
PubMed
Reference # 56047213
PubMed
Amino Acid Substitution: R1138C
cDNA Position: 3412 c→t (exon 21)
Disease Genetics Frequency Reference
PEO Found in trans w/ A467T (Wong et al., 2008)
PubMed
SANDO Found in trans with A67T in a 35 y.o. with PEO, ataxia, sensory neuropathy, muscle weakness, and Chorea. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: R1142W
cDNA Position: 3424 c→t (exon 21)
Disease Genetics Frequency Reference
Neutral polymorphism 0.6% of 450 individuals (GeneSNPs, 2004)
PubMed
Reference # rs2307442
PubMed
Amino Acid Substitution: E1143G
cDNA Position: 3428 a→g (exon 21)
Disease Genetics Frequency Reference
Neutral polymorphism Neutral polymorphism but may modulate disease mutations SNP at 3.7% of 450 individuals of European descent. Not found in Asian or African populations  (GeneSNPs, 2004) 
PubMed
PEO Found as a heterozygous mutation Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians (Di Fonzo et al., 2003)
PubMed
Ataxia Found as a homozygous and heterozygous mutation, or in compound w/ W748S all within the same family (Van Goethem et al., 2004)
PubMed
Alpers found in compound with W748S and Y1210fs1216X, (Ferrari et al., 2005)
PubMed
Neutral polymorphism but may modulate disease mutations Found in cis w/ A889T (Hisama et al., 2005) 
PubMed
Ataxia Found as a homozygous mutation w/ W748S Carrier frequency in the general Finnish population of 1:125 from 500 control chromosomes (Hakonen et al., 2005)
PubMed
Alpers Found in trans w/G848S and in cis w/E1143G in 4 children w/ hepatocerebral disorders and mtDNA depletion Present in 3-5% of the control population (Davidzon et al., 2005)
PubMed
Alpers Found in ataxia-neuropathy in cis with W748S and in compound with G848S or A467T.  (Nguyen et al., 2005)
PubMed
Ataxia Found in compound w/ Q497H and W748S frequency of 0.03 (Winterthun et al., 2005) 
PubMed
Ataxia-neuropathy spectrum disorders Studied the biochemical effects of E1143G in cis with other pathogenic mutations, and how it can modulate the effects of these mutations (Chan et al., 2006)
PubMed
Liver failure, Neuropathy, and PEO Found in trans w/ A467T/T885S and in cis w/ Q789H in an 2.5 y.o. old male with liver failure. Also found in trans w/A467T in a 15 y.o. male w/ PEO. Found in trans w/ S433C in a 25 y.o. male w/PEO. Found in cis w/ L965X and in trans w/ R627Q/Q1236H in a PEO patient. Found in trans w/G 517V in a 4 y.o. female and her father both w/ ataxia and neuropathy. Not found in 250 control individuals (Horvath et al., 2006)
PubMed
Encephalopathy Found in compound w/ W748S, A467T R323H, and M1163R in children w/ progressive encephalopathy Not found in 200 control alleles (Kollberg et al., 2006)
PubMed
Alpers Found in compound w/ W748S and nt2842_2843insA in children w/ multiple complex deficiencies Sarzi, et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation W748S with E1143G. (Sarzi, et al. 2007)
PubMed
Alpers with valproate-induced hepatic failure Found in cis w/ T885S and A467T, and in trans w/ Q879H (McFarland et al., 2008)
PubMed
Alpers, Ataxia Neuropathy, and arPEO+ Myocerbrohepatopathy (MCHS) Found in trans w/ G848S, and in cis w/Q497H-W748S.  Also found in trans w/ A467T, and in cis w/ Q497H-W748S. Also in cis w/ E1143 and in trans w/ G737R in MCHS. (Wong et al., 2008)
PubMed
PEO and Ataxia Found in cis w/ G746S and in trans w/ G848S. In a 2nd pt., found in cis w/W748S and in trans w/ G11D and R852C. (Stewart et al., 2009)
PubMed
mtDNA depletion In cis w/ W748S and in trans w/ H1110Y+Q1236H (Taanman et al., 2008)
PubMed
Alpers In cis w/W748S and in trans w/G848S (Taanman et al., 2008)
PubMed
Alpers Found in cis w/ Q497H and W748S, and in trans w/ G848S. Found in one child with a normal brain MRI. (Brunetti-Pierri et al., 2008)
PubMed
Lipodystrophy Increase susceptibility of HIV pt. treated w/D4T to develop lipodystrophy (Chiappini, et al., 2009)
PubMed
PEO, ptosis, polyneuropathy, ataxia, and dysarthria Found in compound w/ A467T and W748S <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Epilepsy and myoclonic ar, found w/ A467T <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
Reference # rs2307441
PubMed
SANDO Found in trans with A467T and in cis with W748S. Sensory ataxia, dysarthria, and opthalmoplegia. (Posada et al., 2010)
PubMed
Alpers Found in cis with W748S and in trans with R807C in a 1y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Alpers Found in cis with Q497H and W748S, and in trans with A467T in a 6 y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Alpers Found in cis with W748S and in trans with G8484S in a 11 mo. old with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
Alpers Found in cis with W748S and in trans with T914P in a 2.5 y.o. with epilepsy and encephalopathy 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples (Isohanni et al., 2011)
PubMed
VPA-induced liver toxicity Found in 2 patients ages 26 and 33 with VPA-induced hepatotoxicity as a heterozygous mutation A frequency 1.9x10e-4 out of 968 alleles of ethnically matched population controls (Stewart et al., 2010)
PubMed
Alpers Found w/R232H and W748S in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Alpers Found w/M1163R and W748S in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
MIRAS Mother and son were homozygous for W748S in cis with E1143, and the unaffected father was heterozygous for W748S in cis with E1143G. Both mother and son had decreased mtDNA and spinocerebellar ataxias with presentation in late 30's and early 40's. Frequencies in Europe for W748S+E1143G or A467T range from 0.6% in Belgium, 0.8% in Finland, and 2% in Finland (Palin et al., 2012)
PubMed
Alpers Found w/W748S in a 16 mo. boy with epilepsy, mtDNA depletion, and noted defects of the respiratory chain complexes I,II, and IV. (de Camaret et al., 2014)
PubMed
PEO Found in compound w/A143V and W748S in a 40 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
Inclusion body myositis Found as a heterozygous mutation in a Swedish patient with Inclusion body myostitis. In addition the patient had COX deficient muscle fibers, ragged red fibers, and mtDNA deletions. 1 in 26 patients with inclusion body myositis. 8 of which had heterozygous POLG mutations. (Lindgen et al., 2015)
PubMed
SCAE Found in trans wW748S on both allels in a 22 y.o. with cerebellar ataxia, seizures, deafness, migraines, and dystonia (Bereau et al., 2016)
PubMed
SCAE Found in trans with A467T and in cis W748S in a 36 y.o. with PEO, ataxia, sensory neuropathy, seizures, and migraines. (Bereau et al., 2016)
PubMed
SANDO Found in cis w/W748S and in trans w/R627Q and Q1236H in a 38 y.o. with sensory neuropathy, ataxia, PEO, and cognitive impairment. (Bereau et al., 2016)
PubMed
SANDO Found in trans w/R627Q and Q1236H and in cis w/W748S in a 47 y.o. with sensory neuropathy, ataxia, Ophthalmoparesis and muscle weakness. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: D1145GfsX9
cDNA Position: gagg ins at 3433 /3434 (exon 21)
Disease Genetics Frequency Reference
Seizures Found in trans w/ L304R in a 12 y.o. with hypotonia and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: R1146C
cDNA Position: 3436 c→t (exon 21)
Disease Genetics Frequency Reference
Neutral polymorphism SNP 0.6% of 450 individuals (GeneSNPs, 2004)
PubMed
Neutral polymorphism Found as a heterozygous mutation in a 18 y.o. male with muscle atrophy 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez-Vioque et al., 2006)
PubMed
Reference # rs2307440
PubMed
Amino Acid Substitution: N1157S
cDNA Position: 3470 a→g (exon 21)
Disease Genetics Frequency Reference
? Found in trans w/ T251I and P587L in a 9 y.o. w/ no symptoms noted Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: c.3482 +2t>c
cDNA Position: 3482 +2t's splice at intron 21 (exon 21)
Disease Genetics Frequency Reference
Alpers Exon21/Intron21 splice site mutation at a.a. 1161. Found in trans with A467T in a male child w/ infantile hepatocerbral syndrome (Ferrari et al., 2005)
PubMed
Amino Acid Substitution: c.3626_3629dupGATA
cDNA Position:
Disease Genetics Frequency Reference
Alpers Found in a 1 y.o female with , located 14nt befoer the end of exon 22 resulting in the in a premature stop codon and the skipping of most of exon 22. (de Camaret et al., 2014)
PubMed
Amino Acid Substitution: M1163R
cDNA Position: 3488 t→g (exon 22)
Disease Genetics Frequency Reference
Liver failure, encephalopathy, and epilepsy Found as compound in trans with W748S - E1143G Not found in 200 control alleles (Kollberg et al., 2006)
PubMed
Alpers Found w/E1143G and W748S in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement (Sofou et al., 2012)
PubMed
Amino Acid Substitution: F1164I
cDNA Position: 3490 t→a (exon 22)
Disease Genetics Frequency Reference
PEO Ar, found in cis with T914P and in trans with Q308H Not found in 200 Italian controls (Horvath et al., 2006)
PubMed
PEO Found in trans w/M1057T in a71 y.o. with Ophthalmoparesis, ptosis, depression, and muscle weakness. (Bereau et al., 2016)
PubMed
Amino Acid Substitution: F1164L
cDNA Position: 3492 t→ g or a (exon 22)
Disease Genetics Frequency Reference
Reference # rs62640038
PubMed
Amino Acid Substitution: L1173fsX
cDNA Position: 3518 ins gact, fs in exon 22 (exon 22)
Disease Genetics Frequency Reference
Alpers Compound with A467T Not found in 300 control chromosomes (Nguyen et al., 2006)
PubMed
Amino Acid Substitution: Q1175R
cDNA Position: 3524 a→g (exon 22)
Disease Genetics Frequency Reference
SNP Reference # rs188348569
PubMed
Amino Acid Substitution: S1176L
cDNA Position: 3527 c→t (exon 22)
Disease Genetics Frequency Reference
PEO Found as a heterozygous mutation Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians (Lamantea et al., 2002)
PubMed
PEO Found in compound w/with T251I/P587L (Lamantea and Zeviani, 2004)
PubMed
Amino Acid Substitution: D1184L
cDNA Position: 3550 g→c (exon 22)
Disease Genetics Frequency Reference
PEO Found as a compound heterozygote with S998L in a 64 y.o. female with PEO, bilateral ptosis, and encephalopathy. (Martikainen et al., 2010)
PubMed
Amino Acid Substitution: D1184N
cDNA Position: 3550 g→a (exon 22)
Disease Genetics Frequency Reference
PEO and tetraparesis Compound in trans with N468D 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez - Vioque et al., 2006)
PubMed
Multi-system disorder Found in compound with R227W in 2 children w/ severe childhood multi-system disorder de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder (de Vries et al., 2007)
PubMed
Failure to thrive ar, found in trans w/ S1095R. Aslo, impaired liver functions, deafness, and demyelating sensomotor neuropathy <0.5% in Dutch population (Blok and van den Bosch et al., 2009)
PubMed
PEO Found as a heterozygous mutation in a 70 yo male with PEO, neuronopathy, and parkinsonism Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
PEO Found as a heterozygous mutation in a 75 yo male with PEO and neuronopathy Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
PEO Found in compound w/T251I and P587L in a 33 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
PEO Found in compound w/P587L and T251I in a 30 y.o. male patient w/ chronic intestinal pseudo-obstruction and PEO. In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction (Amiot et al., 2009)
PubMed
Amino Acid Substitution: I1185T
cDNA Position: 3554 t→c (exon 18)
Disease Genetics Frequency Reference
Myocerebrohepatopathy spectrum disorder Found in compound w/A957V in an 8 mo. Japanese female. Hypotonia, failure to thrive, hepatomegaly, and developmental regression. Hetero compound not found in 1000 Genome Project, ESP6500 data base, nor HGVD (Montassir, et al., 2014)
PubMed
Amino Acid Substitution: I1185N
cDNA Position: 3554 t→a (exon 18)
Disease Genetics Frequency Reference
Progressive ataxia and Palatal tremor (PAPT) Found in trans w/W748S in a 52 y.o. male w/ kinetic and static ataxia, dysarthria, palatal trmor, and vertical nystagmus. (Nicastro et al., 2016)
PubMed
Amino Acid Substitution: R1187W
cDNA Position: 3559 c→t (exon 22)
Disease Genetics Frequency Reference
Found in a patient with mitochondrial depletion syndrome and T cell immunodeficiency. Pathogenesis unclear. Not detected in 100 Turkish control alleles (Reichenbach et al., 2006)
PubMed
Hepatic failure Found as a heterozygous mutation in a 10 yo male with hepatic failure, myopathy and psychomotor delay Found in 160 French cohort of potential POLG patients (Rouzier et al., 2013)
PubMed
Amino Acid Substitution: C1188R
cDNA Position: 3562 t→c (exon 22)
Disease Genetics Frequency Reference
Seizures Found in trans w/ A467T in a 3 y.o. w/ seizures, hypotonia, and developmentally delayed Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: K1191N
cDNA Position: 3573 g→t (exon 22)
Disease Genetics Frequency Reference
Alpers Compound in trans with A467T Not found in 250 control individuals (Horvath et al., 2006)
PubMed
PEO Found in trans w/ T251I and P587L in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: K1191R
cDNA Position: 3572 a→g (exon 22)
Disease Genetics Frequency Reference
Myocerebrohepatopathy In trans with T251I-P587L (Wong et al., 2008)
PubMed
Amino Acid Substitution: D1196N
cDNA Position: 3586 g→a (exon 22)
Disease Genetics Frequency Reference
Myopathy In trans w/ G517V (Wong et al., 2008)
PubMed
Amino Acid Substitution: T1199X
cDNA Position: 3595 ins. a (exon 22)
Disease Genetics Frequency Reference
Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Found with R627Q in a 47 yr. old patient (Schulte et al., 2009)
PubMed
Amino Acid Substitution: c.3600 del T
cDNA Position: 3600 deletion of t (exon 22)
Disease Genetics Frequency Reference
Epilepsy Found with W748S in a 3 y.o. female. Patient also had myopathy. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. (Sitarz et al., 2014)
PubMed
Amino Acid Substitution: G1205A
cDNA Position: 3614 g→ c (exon 22)
Disease Genetics Frequency Reference
Heterozygous w/ Retinitis pigmentosa, hearing loss, failure to thrive (Wong et al., 2008)
PubMed
Amino Acid Substitution: Y1210fs1216X
cDNA Position: 3630 ins c (exon 22)
Disease Genetics Frequency Reference
Alpers Found in compound with W748S and E1143G, Mutation causes frame shift to stop at a.a. 1216. (Ferrari et al., 2005)
PubMed
Alpers Found in 2 infants in compounds w/ W748S (Spinazzola et al., 2009)
PubMed
Amino Acid Substitution: Q1214X
cDNA Position: 3640 c→t (exon 22)
Disease Genetics Frequency Reference
PEO Found in trans w/ S933R in a 60 y.o. w/ PEO, dementia, myopathy, and abnormal muscle histology Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011)
PubMed
Amino Acid Substitution: c.3643+2t>c
cDNA Position: 3645 t→c splice variant(exon 22/23)
Disease Genetics Frequency Reference
Alpers Found in trans w/ A467T (Roels, et al., 2009)
PubMed
Amino Acid Substitution: S1230F
cDNA Position: 3689 c→t (exon 23)
Disease Genetics Frequency Reference
Neutral polymorphism <1 % in control populations (Luoma et al., 2007)
PubMed
Found in a Chinese population with Parkinsonism at an allelic frequency of 0.453 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
Amino Acid Substitution: Q1236H
cDNA Position: 3708 g→t (exon 23)
Disease Genetics Frequency Reference
Neutral polymorphism 4.0% of 450 individuals (GeneSNPs, 2004) 
PubMed
Neutral polymorphism Found in 5 PEO patients as a heterozygous mutation Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians (Di Fonzo et al., 2003) 
PubMed
Neutral polymorphism Found in cis with R627Q in trans with A467T in a family w/ ataxia - myopathy and ptosis (Luoma et al., 2005)
PubMed
Alpers Found in trans with A467T, and in cis w/ T849H. Also found as a compound w/ R1096C. (Wong et al., 2008)
PubMed
mtDNA depletion In cis w/ H1110Y and in trans w/ E1143G+W748S (Taanman et al., 2008)
PubMed
Reference # rs3087374
PubMed
VPA induced liver toxicity Found in 5 patients ages 2 to 47 with VPA-induced hepatotoxicity as a heterozygous mutation A frequency 1.9x10e-4 out of 968 alleles of ethnically matched population controls (Stewart et al., 2010)
PubMed
Found in a Chinese population with Parkinsonism at an allelic frequency of 0.281 344 Chinese parkinson patients and 144 controls (Gui et al., 2012)
PubMed
Sensory axonal neuronopathy Found in a 67 y.o. female and her 61 y.o. brother. Found in compound w/Y837C, D122Y, K601E. Both patients have an ataxia, dysarthria, seizures, and sensory neuropathies. Not found in 200 chromosomes controls (Zabalza et al., 2014)
PubMed
Inclusion body myositis Found as a heterozygous mutation in 5 unrelated Swedish patients with Inclusion body myostitis. All patients had COX deficient muscle fibers, ragged red fibers, and mtDNA deletions. 5 in 26 patients with inclusion body myositis. 8 of which had heterozygous POLG mutations. (Lindgen et al., 2015)
PubMed
SANDO Found in cis w/R627Q and in trans w/W748S and E1143G in a 38 y.o. with sensory neuropathy, ataxia, PEO, and cognitive impairment. (Bereau et al., 2016)
PubMed
SANDO Found in cis w/R627Q and in trans w/W748S and E1143G in a 47 y.o. with sensory neuropathy, ataxia, Ophthalmoparesis and muscle weakness. (Bereau et al., 2016)
PubMed
Progressive multi-systemic disorder Found in cis w/Y955H in an 8 month old with weight loss, hearing loss, myopathy, liver failure, decreased ATP production, COX negative muscle fibers, and ragged red fibers. (Siibak et al., 2017)
PubMed
PEO Found in trans w/G517V in a 23 y.o. with PEO and hypostenia. (Pozzo et al., 2017)
PubMed
Amino Acid Substitution: X1240Q+35a.a.
cDNA Position: 3718 t→c +35aa (exon 23)
Disease Genetics Frequency Reference
PEO Found in trans w/A467T in a 50 y.o. male with arPEO and sensory neuropathy (Lax et al., 2012b)
PubMed
Amino Acid Substitution: X1240Y+35a.a.
cDNA Position: 3720 g→c +35aa (exon 23)
Disease Genetics Frequency Reference
PEO Found in trans w/A467T in a 42 y.o. female with PEO, ptosis and sensory neuropathy (Lax et al., 2012a)
PubMed
 

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