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National Institute of Environmental Health Sciences

 

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.


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diagram of POLG mutations

Visual overview of the POLG mutations.


Amino Acid Substitution cDNA position Disease Details Frequency Reference Link to PubMed
R3P 8 g→c (exon 2) PEO ar (Van Goethem et al., 2001) reported 0 out of 229 control Individuals (<0.4%) (Van Goethem et al., 2001) PubMed
G11D 32 g→a (exon 2) 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
P18S 52 t→g (exon 2) Neutral polymorphism 0.6% of 450 individuals (GeneSNPs, 2004) PubMed
S28C 82 a→t (exon 2) 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
R42X 125 del (exon 2) Reference # rs59510277 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=59510277 PubMed
±Glu at aa 43-52 ±(CAG)n at nucleotides 126 to 157 (exon 2) 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
Q43R 128 a→g (exon 2) Idiopathic sporadic Parkinson (Luoma et al., 2007) PubMed
Reference # rs28567406 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=28567406 PubMed
Q44X 132 del gc (exon 2) Reference # rs35424491 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=35424491 PubMed
Q45R 134 a→g (exon 2) Epilepsy Found in trans w/ D136E <0.5% in Dutch population (Blok and van den Bosch et al., 2009) PubMed
Q49E 145 c→g (exon 2) Neutral polymorphism <1 % in control populations (Luoma et al., 2007) PubMed
Q49X 147 del gc (exon 2) Reference # rs72434227 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=72434227 PubMed
Q50X 149 del ag (exon 2) Reference # rs71879812 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=71879812 PubMed
Q53X 158 del aa (exon 2) Reference # rs41550117 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=41550117 PubMed
S64L 191 c→t (exon 2) Found in cis with R232H in ar Charcot-Marie-Tooth 30.6% of control population (90/294 control alleles) (Harrower et al, 2008) PubMed
Q68X 202 c→t (exon 2) Alpers Found in trans w/ A467T (Wong et al., 2008) PubMed
L79F 235 c→t (exon 2) 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
L83P 248 t→c (exon 2) Alpers Compound heterozygous mutation with G888S in 10 yr. old (Bao et al., 2008) PubMed
(Wong et al., 2008) PubMed
F88L 264 c→g (exon 2) 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
H110Y 328 c→t (exon 2) Heterozygous, hypotonia, failure to thrive, short stature, respiratory failure (Wong et al., 2008) PubMed
W113G 337 t→g (exon 2) Reference # rs77321104 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=77321104 PubMed
D136E 408 c→g (exon 2) Epilepsy Found in trans w/ Q45R <0.5% in Dutch population (Blok and van den Bosch et al., 2009) PubMed
A143V 427 g→t (exon 2) 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
P163S 487 c→t (exon 2) 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
E183X 547 del g (exon 2) Reference # rs35065786 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=35065786 PubMed
R193Q 578 g→a (exon 2) Neutral polymorphism 0.6% of 450 individuals (GeneSNPs, 2004) PubMed
Reference # rs3176162 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=3176162 PubMed
C224Y 671 g→a (exon 3) 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
R227W 679 c→t (exon 3) 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
R227P 680 g→c (exon 3) 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
R232G 694 c→g (exon 3) 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
R232H 695 g→a (exon 3) 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
697 g→a (exon 3) Leigh Syndrome In trans w/G848S (Taanman et al, 2008) PubMed
695 g→a (exon 3) 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
697 g→a (exon 3) 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
W235X 705 g→a (exon 3) 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
Q238R 713 a→g (exon 3) Reference # rs56410699 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=56410699 PubMed
P241L 722 c→t (exon 3) Neutral polymorphism <1 % in control populations (Luoma et al., 2007) PubMed
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
L244P 731 t→c (exon 3) 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
T251I 752 c→t (exon 3) 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
G268A 803 g→c (exon 3) 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 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=61752784 PubMed
R275X 823 c→t (exon 3) PEO and mental retardation Found in trans w/ T251I+P587L <0.5% in Dutch population (Blok and van den Bosch et al., 2009) PubMed
R275Q 824 g→a (exon 3) Multiple Sclerosis-like illness 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
H277L 830 a→t (exon 3) 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
Y282D 844 t→g (exon 3) 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
G303R 907 a→g (exon 4) 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
L304R 911 t→g (exon 4) 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
S305R 915 c→g (exon 4) 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
Q308H 924 g→c (exon 4) PEO Found in trans w/W748S Not found in 250 control individuals (Horvath et al., 2006) PubMed
R309L 926 g→t (exon 4) PEO ar, Compound with T251I Not found in 100 DNA samples (Lamantea et al., 2002) PubMed
R309H 926 g→a (exon 4) Alpers Compound in trans with R627Q Not found in 250 control individuals (Horvath et al., 2006) PubMed
W312R 934 t→c (exon 4) 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
K319E 955 a→g (exon 4) 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
P324S 970 t→g (exon 4) Neutral polymorphism 0.6% of 450 individuals (GeneSNPs, 2004) PubMed
Reference # rs2307437 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307437 PubMed
T326fs61X 975-976 ins c stop@387 (exon 4) 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
S332X 994 del c or tc→g (exon 4) Reference # rs35954915 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=35954915 PubMed
W347_L356 del 1039-1068 del (exon 5) Alpers 10 amino acid del found in trans w/A467T (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed
E358A 1073 a→c del364X (exon 4) Alpers Found in trans w/A467T in a 3 y.o. w/seizures, ataxia, and developmentally delayed (Hunter et al., 2011) PubMed
1073 a→c del364X (exon 4) Alpers Found in trans w/A467T in a 4 y.o. w/seizures, ataxia, and developmentally delayed (Hunter et al., 2011) PubMed
R374X 1120 c→t (STOP) (exon 5) Alpers Found in trans w/A467T. (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed
G380D 1139 g→a (exon 5) 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
R386C 1156 c→t (exon 5) 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
R386H 1157 g→a (exon 5) Alpers Heterozygous single mutation found in a 1 y.o.. (Baruffini et al., 2011) PubMed
L392V 1174 c→g (exon 6) 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
L392W 1174 ct→tg (exon 6) 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
R417T 1250 g→c (exon 6&7 junction) Alpers Found in trans w/A467T (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed
Exon 7 deletion c.1251-2 a→t (exon 6&7 splice site) 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
C418R 1252 t→c (exon 7) 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
L424GfsX28 1270-1271 del ct stop @ 452 (exon 7) 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
G426S 1276 g→a (exon 7) 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
L428P 1283 t→c (exon 7) 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
M430L 1288 a→t (exon 7) 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
G431V 1292 g→t (exon 7) 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
S433C 1298 c→g (exon 7) 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
Q449X 1345 c→t (exon 7) 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
Y452X 1356 t→g (exon 7) 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
L463F 1389 g→t (exon 7) 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
M464T 1391 t→c (exon 7) 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
A467T 1399 g→a (exon 7) 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 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
N468D 1402 a→g (exon 7) PEO Found in compound w/A1105T in a family w/PEO Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes. (Luoma et al., 2004) PubMed
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
c. 1433 +1g→a 1433 ins g→a (Splice variant between ex 7 and ex 8) 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
Y479X 1433 large del (exon 8) Reference # rs71653298 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=71653298 PubMed
Q497H 1491 g→c (exon 8) 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
S511N 1532 g→a (exon 8) 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
K512M 1535 a→t (exon 8) Parkinsonism Found as a heterozygous mutation in a 79 yo male with PEO and parkinsonism (Dulhon et al., 2013) PubMed
G517V 1550 g→t (exon 8) 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
R546C 1636 c→t (exon 9) Neutral polymorphism 1% 1.1% of 450 individuals (GeneSNPs, 2004) PubMed
Heterozygous with R628Q in one breast tumor (Singh et al, 2009) PubMed
Reference # rs2307447 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307447 PubMed
R546S 1636 c→a (exon 9) Reference # rs2307447 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307447 PubMed
R546G 1636 c→g (exon 9) Reference # rs2307447 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307447 PubMed
K561M 1882 a→t (exon 9) 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
R562Q 1685 g→a (exon 9) PEO sporadic Not found in 100 DNA samples from healthy Italians (Di Fonzo et al., 2003) PubMed
H569Q 1707 c→(a or g) (exon 9) Homozygous (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed
R574W 1720 c→t (exon 10) 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
R579W 1735 c→t (exon 10) PEO Sporadic / unknown Compound with A889T Not detected in 120 healthy control alleles (Filosto et al., 2003) PubMed
W585X 1754 g→a (exon 10) 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
P587L 1760 c→t (exon 10) 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
G588D 1763 g→a (exon 10) 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
P589L 1766 c→t (exon 10) Alpers Found in cis w/P587L and in trans w/W748S. (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed
L591F 1774c→t (exon 10) SANDO Found in trans w/R1096C in a 48 y.o. female with SANDO and dysphagia. (Kurt et al., 2012) PubMed
R597W 1789 c→t (exon 10) 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
M603L 1807 a→t (exon 10) 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
L605R 1814_1815 tt→gc (exon 10) Alpers Found in trans w/ A467T. Mitochondria depletion in liver (Stewart et al., 2009) PubMed
Y614X 1842 c→ a or g Reference # rs62640033 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640033 PubMed
R617C 1849 c→t (exon 10) Heterozygous with muscle weakness, exercise intolerance, hearing loss, arrhythmia (Wong et al., 2008) PubMed
L623W 1868 t→g (exon 10) Hypoketotic, hypyoglycaemial, and liver dysfunction Compound heterozygote w/ K755E Not found in 200 healthy controls (Bortot, et al., 2009) PubMed
P625R 1874 c→g (exon 10) Alpers Found as a compound heterozygote w/ A467T in a 1 y.o. with epilepsy and liver failure. (Baruffini et al., 2011) PubMed
R627W 1879 c→t (exon 10) 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
R627Q 1880 g→a (exon 10) 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
R628Q 1883 g→a (exon 10) Mutation found in one breast tumor heterozygous w/ the SNP R546C (Singh et al., 2009) PubMed
P648R 1943 c→g (exon 10) 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
H659Q 1977 c→g (exon 11) Reference # rs62640030 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640030 PubMed
E662K 1984 g→a (exon 11) Neutral polymorphism 2.8% of 450 individuals (GeneSNPs, 2004) PubMed
Q666L 1997 a→t (exon 11) Reference # rs62640029 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640029 PubMed
R709X 2125 c→t (exon 12) 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
Q715X 2143 c→t (exon 12) 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
c.2157+5_+6gc>ag 2157 gc→ ag (exon 12) Alpers Found in trans with A467T, most likely a splice site mutation. (Wong et al., 2008) PubMed
R722H 2165 g→a (exon 13) 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
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
H734R 2201 a→g (exon 13) Reference # rs56119329 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=56119329 PubMed
N736S 2207 a→g (exon 13) Ataxia, cardiomyopathy, and depression Found in a 52 y.o. female with melancholic depression, unstable gailt, and dilated cardiomyopathy. (Verhoeven et al., 2011) PubMed
G737R 2209 g→c (exon 13) 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
2210 g→c (exon 13) 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
N740D 2218 a→g (exon 13) Reference # rs78347903 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=78347903 PubMed
V742M 2224 g→a (exon 13) SNP Reference # rs147827654 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusID=5428 PubMed
G746S 2236 g→a (exon 13) 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
W748S 2243 g→c (exon 13) Ataxia Found in compound w/E1143G w/ataxia, dysarthria, and cognitive impairment. Also found as a homozygous mutation. (Van Goethem et al., 2004)  PubMed
Infantile Hepatocerebral Syndrome Found in trans w/ Y1210fs1216X and also in trans w/ L244P 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/G8484S. (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
F749S 2246 t→c (exon 13) 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
L752P 2255 t→c (exon 13) Epilepsy, seizures, VPA induced liver failure Found in trans w/W748S and E1143G (Zsurka, et al., 2008) PubMed
H754Q 2262 c→g (exon 13) 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
K755E 2263 g→a (exon 13) Hypoketotic, hypyoglycaemial, and liver dysfunction Compound heterozygote w/ L623W Not found in 200 healthy controls (Bortot, et al., 2009) PubMed
G763R 2287 g→c (exon 14) PEO, SANDO ar, Found as a homozygous mutation in PEO-SANDO Not found in 500 ethnically-matched control chromosomes (Santoro et al., 2006) PubMed
P765T 2293 c→a (exon 14) 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
A767D 2300 c→a (exon 14) 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
K768E 2302 a→g (exon 14) 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
G785fs21X 2354 ins g stop @ 806 (exon 14) PEO ar, Compound with T251I Absent in 100 control DNA samples (Lamantea et al., 2002) PubMed
R790H 2369 g→a (exon 14) SNP Reference # rs191490663 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusID=5428 PubMed
M797del 2391-2393 gat de (exon 14) 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
A804T 2410 g→a (exon 14) 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
R807H 2420 g→a (exon 14) 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
R807P 2420 g→c (exon 14) 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
R807C 2419 c→t (exon 14) 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
4.7kb deletion of exons 15-21 Intronic deletion starting in intron 14 (87,662,154) thru intron 21 (87,666,650), excising exons 15-21. 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
c. 2480+1g>a 2480+1 g→a splice site (exon 15) Alpers Found in trans w/ W748S-E1143G (Wong et al., 2008) PubMed
IVS15-9- c.2485del 12bp 2485 del 12bp (exon 16) Alpers Splice site mutation 3'exon15/intron junction, Found in trans with A467T Not found in 250 control individuals (Horvath et al., 2006) PubMed
IVS16-10 c>t IVS16-10 c>t (exon 16) Cerebellar ataxia, sensory neuropathy, and dysphagia Homozygous. Found in a 60 y.o. patient (Schulte et al., 2009) PubMed
Y831F 2492 a→t (exon 16) Reference # rs41549716 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=41549716 PubMed
Y831S 2492 a→c (exon 16) Reference # rs41549716 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=41549716 PubMed
Y831C 2492 a→g (exon 16) 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
G848S 2542 g→a (exon 16) 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 5 y.o. 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
T849H 2544 (insertion of c with fs868X) (exon 16) Alpers Found in trans with A467T and in cis with Q1236H (Wong et al., 2008) PubMed
T851A 2551 a→g (exon 16) 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
R852C 2554 c→t (exon 16) 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
R852H 2555 g→a (exon 16) 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
R853W 2557 c→t (exon 16) 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
R853Q 2558 g→a (exon 16) Myocerebrohepatopathy In trans with T251I-P587L (Wong et al., 2008) PubMed
V855L 2563 g→t (exon 16) 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
V855A 2564 t→c (exon 16) Heterozygous with muscle weakness. (Wong et al., 2008) PubMed
A862T 2584 g→a (exon 16) Ataxia Neuropathy Compound heterozygous with R964C (Wong et al., 2008) PubMed
PEO with ataxia In trans w/R1047W (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
N864S 2591 a→g (exon 16) PEO Found as compound with T251I-P587L Not found in 280 control chromosomes (Van Goethem et al., 2003c) PubMed
IVS16-10 c>t IVS16-10 c>t (exon 16) Cerebellar ataxia, sensory neuropathy, and dysphagia Homozygous. Found in a 60 yr. old patient (Schulte et al., 2009) PubMed
R869Q 2606 g→a (exon 17) 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
E873X 2617 g→t (exon 17) 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
Q879H 2637 g→t (exon 17) 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
T885S 2653 a→t (exon 17) 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
L886P 2657 t→c (exon 17) Alpers Found in trans w/ A467T (Wong et al., 2008) PubMed
G888S 2662 g→a (exon 17) Alpers Compound heterozygous with L83P in 10 yr. old (Bao et al., 2007) (Wong et al., 2008) PubMed
G888D 2663 g→a (exon 17) 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
A889T 2665 g→a (exon 17) 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
D892GfsX39 2675 ins g (exon 17) 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
E895G 2684 a→g (exon 17) Myopathic MDS Found in one newborn with floppiness and 20% liver mtDNA depletion, heterozygous (Spinazzola et al., 2009) PubMed
T914A 2740 a→g (exon 18) 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
T914P 2740 a→c (exon 18) 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
W918R 2752 t→c(exon 18) 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
G923D 2768 g→a (exon 18) 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
G923R 2767 c→g (exon 18) Reference # rs60636456 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=60636456 PubMed
K925R fs42X 2772_2773 delG 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
D930N 2788 g→a (exon 18) Alpers Infantile Alpers w/ bilateral lesions of thalami. Hepatocerebral MDS patient, Found in trans w/ W748S. (Spinazzola et al., 2009) PubMed
H932Y 2794 c→t (exon 18) 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
S933R 2799 t→g (exon 18) 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
R943C 2827 c→t (exon 18) Myocerebrohepatopathy In cis w/ E1143G and in trans w/G737R (Wong et al., 2008) PubMed
PEO Ad, and premature ovarian failure <0.5% in Dutch population (Blok and van den Bosch et al., 2009) PubMed
R943H 2828 g→a (exon 18) 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
K947R 2840 g→a (exon 18) PEO and ovarian failure Compound heterozygote found w/ expansion of a polyQ (18Q) stretch. (Baruffini et al., 2011) PubMed
Y951N 2851 t→a (exon 18) 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
R953C 2857 c→t (exon 18) PEO ad Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes. (Luoma et al., 2004) PubMed
Reference # rs11546842 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=11546842 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
Y955C 2864 a→g (exon 18) 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
A957S 2869 g→t (exon 18) 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
A957P 2869 g→c (exon 18) 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
A957V 2870 c→t (exon 18) 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
F961S 2882 t → c (exon 18) PEO ad PEO (Adachi et al., 2002) PubMed
A962T 2884 g→a (exon 18) 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
R964C 2890 c → t (exon 18) 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
L965X 2894 t→g (exon 18) PEO ar, found in cis with E1143G and in trans with R627Q-Q1236H Not found in 250 control individuals (Horvath et al., 2006) PubMed
L966R 2897 t→g (exon 18) 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
G975stop 2923 c→t (exon 18) 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
S998W 2993 c→g (exon 19) Reference # rs79840247 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=79840247 PubMed
S998L 2993 c→t (exon 19) PEO Found as a compound heterozygote with D1184H in a 64 y.o. female with PEO, bilateral ptosis, and encephalopathy. (Martikainen et al.,) PubMed
W1020X 3057 g→a (exon 19) Alpers Compound with A467T (Nguyen et al., 2005) PubMed
Q1024X 3067 c→t (exon 20) 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
c. 3104 +3a→t 3104 +3a→t (splice variant between ex. 19 and 20) 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
3104 +3a→t (splice variant resulting in a deletion on exon 19) 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
V1044A 3131 t→c (exon 20) 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
R1047Q 3140 g→a (exon 20) PEO Sporadic / unknown Not found in 250 control individuals (Agostino et al., 2003) PubMed
R1047W 3139 c→t (exon 20) Alpers Compound in trans with T851A Not found in over 200 control alleles (Wiltshire et al., 2008) PubMed
PEO ar, in trans w/ A862T (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
K1050RfsX44 3149 del a (exon 20) 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
G1051R 3151 g→c (exon 20) PEO, SANDO ar Found as compound with H932Y not seen in 120 control subjects. (Mancuso et al., 2004a) PubMed
P1073L 3218 c→t (exon 20) 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
G1076V 3227 g→t (exon 20) PEO Sporadic / unknown Not detected in 120 healthy control alleles (Filosto et al., 2003) PubMed
C1077G 3229 t →g (exon 20) 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
I1079L 3235 a→c (exon 20) adPEO Heterozygous Hearing loss, and ptosis (Wong et al., 2008) PubMed
S1080T 3239 g→c (exon 20) Intracranial calcifications A 55 y.o. female with action tremors, peripheral neuropathy, hearing loss, and intracranial calcifications (Sidirooulos et al., 2013) PubMed
S1080I 3239 g→t (exon 20) 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
R1081dup 3240– 3242 ins ccg (R) (exon 20) 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
R1081Q 3241 c→g (exon 20) 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
R1081P 3242 g→c (exon 21) 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
F1092L 3276 t→g (exon 21) Reference # rs74034411 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=74034411 PubMed
S1095R 3285 c→g (exon 21) adPEO Hearing loss, ptosis, Muscle weakness, optic atrophy (Wong et al., 2008) PubMed
3286 c→g (exon 21) 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
R1096C 3286 c→t (exon 21) 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
R1096H 3287 g→a (exon 21) Alpers Found as a compound in trans with R627Q Not found in 250 control individuals (Horvath et al., 2006) PubMed
S1104C 3311 c→g (exon 21) 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
S1104F 3311 c→t (exon 21) 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
A1105T 3313 g→a (exon 21) 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
V1106I 3316 g→a (exon 21) PEO ar, found in trans with T251I-P587L Not found in 500 Italian controls. (Horvath et al., 2006) PubMed
H1110Y 3328 c→t (exon 21) infantile hepatocerebral mtDNA depletion Heterozygous, found in cis Q1236H, & in trans w/ W748S+ E1143G (Taanman et al., 2008) PubMed
L1113P 3338 t→c (exon 21) 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
R1128H 3383g→a (exon 21) Microcephaly Heterozygous, found w/ G517V (Wong et al., 2008) PubMed
H1134R 3401 a→g (exon 21) infantile hepatocerebral mtDNA depletion Heterozygous, found in trans with Y831C (Taanman et al., 2008) PubMed
E1136K 3406 g→a (exon 21) infantile hepatocerebral mtDNA depletion Heterozygous, found T251I+P587L (Taanman et al., 2008) PubMed
Reference # 56047213 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=56047213 PubMed
R1138C 3412 c→t (exon 21) PEO Found in trans w/ A467T (Wong et al., 2008) PubMed
R1142W 3424 c→t (exon 21) Neutral polymorphism 0.6% of 450 individuals (GeneSNPs, 2004) PubMed
Reference # rs2307442 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307442 PubMed
E1143G 3428 a→g (exon 21) 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
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 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307441 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
D1145GfsX9 gagg ins at 3433 /3434 (exon 21) 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
R1146C 3436 c→t (exon 21) 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 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307440 PubMed
N1157S 3470 a→g (exon 21) ? 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
c.3482 +2t>c 3482 +2t's splice at intron 21 (exon 21) 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
M1163R 3488 t→g (exon 22) 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
F1164I 3490 t→a (exon 22) PEO Ar, found in cis with T914P and in trans with Q308H Not found in 200 Italian controls (Horvath et al., 2006) PubMed
F1164L 3492 t→ g or a (exon 22) Reference # rs62640038 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640038 PubMed
L1173fsX 3518 ins gact, fs in exon 22 (exon 22) Alpers Compound with A467T Not found in 300 control chromosomes (Nguyen et al., 2006) PubMed
Q1175R 3524 a→g (exon 22) SNP Reference # rs188348569 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusID=5428 PubMed
S1176L 3527 c→t (exon 22) 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
D1184L 3550 g→c (exon 22) 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
C1188R 3562 t→c (exon 22) 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
D1184N 3550 g→a (exon 22) 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
R1187W 3559 c→t (exon 22) 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
K1191N 3573 g→t (exon 22) 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
K1191R 3572 a→g (exon 22) Myocerebrohepatopathy In trans with T251I-P587L (Wong et al., 2008) PubMed
D1196N 3586 g→a (exon 22) Myopathy In trans w/ G517V (Wong et al., 2008) PubMed
T1199X 3595 ins. a (exon 22) Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia Found with R627Q in a 47 yr. old patient (Schulte et al., 2009) PubMed
c.3600 del T 3600 deletion of t (exon 22) 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
G1205A 3614 g→ c (exon 22) Heterozygous w/ Retinitis pigmentosa, hearing loss, failure to thrive (Wong et al., 2008) PubMed
Y1210fs6X 3630 ins c (exon 22) Infantile Hepatocerebral Syndrome Compound in trans with W748S - E1143G, Mutation causes frame shift to stop at a.a. 1225 (Ferrari et al., 2005) PubMed
Alpers Found in 2 infants in trans w/ W748S (Spinazzola et al., 2009) PubMed
Q1214X 3640 c→t (exon 22) 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
c.3643+2t>c 3645 t→c splice variant(exon 22/23) Alpers Found in trans w/ A467T (Roels, et al., 2009) PubMed
S1230F 3689 c→t (exon 23) 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
Q1236H 3708 g→t (exon 23) 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
3711 g→t (exon 23) 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 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=3087374 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
X1240Q+35a.a. 3718 t→c +35aa (exon 23) PEO Found in trans w/A467T in a 59 y.o. male with arPEO and sensory neuropathy (Lax et al., 2012b) PubMed
PEO Found in trans w/A467T in a 59 y.o. male with arPEO, ptosis and sensory neuropathy (Lax et al., 2012a) PubMed
X1240Y+35a.a. 3720 g→c +35aa (exon 23) PEO Found in trans w/A467T in a 42 y.o. female with PEO, ptosis and sensory neuropathy (Lax et al., 2012a) PubMed