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Human DNA Polymerase Gamma Mutation Database

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

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

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

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

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

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diagram of POLG mutations

Visual overview of the POLG mutations.

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Amino Acid Substitution cDNA position Disease Details
R3P 8 g→c (exon 2) PEO

Genetics: ar

Frequency: (Van Goethem et al., 2001) reported 0 out of 229 control Individuals (<0.4%)

Reference: (Van Goethem et al., 2001)

Pubmed Link: PubMed

G11D 32 g→a (exon 2) Ataxia Neuropathy

Genetics: Found in cis with R627Q and in trans with R852C, and also found as a Heterozygous mutation with a failure to thrive

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis w/ R852C and in trans w/ W748S. In a second pt. found in cis w/R852C and in trans w/ A467T.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: 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

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

Leigh Syndrome

Genetics: Found in cis with R852C and in trans with W748S

Frequency:

Reference: (Naess et al., 2009)

Pubmed Link: PubMed

Multiple system atrophy

Genetics: Found with R852C in a 58 y.o. female with progressive cerebellar atrophy. Pt. had mtDNA deletions and mtDNA depletion.

Frequency:

Reference: (Mehta et al., 2011)

Pubmed Link: PubMed

Seizures and liver failure

Genetics: Found in trans w/ A467T and in cis w/ R852C in an 8 mo. w/ seizures, liver failure, and lactic acidosis.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in cis w/ R852C and in trans w/ R627Q in a 25 y.o. w/ dementia, encephalopathy, and stroke.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

P18S 52 t→g (exon 2) Neutral polymorphism

Genetics:

Frequency: 0.6% of 450 individuals

Reference: (GeneSNPs, 2004)

Pubmed Link: PubMed

S28C 82 a→t (exon 2) PEO

Genetics: Found in a 25 y.o. pt. that is homozygous for the W748S mutation with PEO, ataxia, ptosis, and hearing loss

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R42X 125 del (exon 2)

Genetics: Reference # rs59510277

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=59510277

Pubmed Link: PubMed

±Glu at aa 43-52 ±(CAG)n at nucleotides 126 to 157 (exon 2) Male infertility

Genetics: Identified an association between absence of the common, ten CAG repeat allele and male infertility due to a range of sperm quality defects.

Frequency: Rovio et al., 2001 reported 88% of both Finnish and ethnically mixed populations carry the predominant allele of 10 CAG repeats

Reference: (Rovio et al., 2001)

Pubmed Link: PubMed

Male infertility

Genetics: 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.

Frequency: 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)

Reference: (Jensen et al., 2004)

Pubmed Link: PubMed

Genetics: The human DNA POL gamma is unique in that the first exon of the gene contains a CAG10 trinucleotide repeat.

Frequency:

Reference: (Ropp and Copeland, 1996) 

Pubmed Link: PubMed

Male infertility

Genetics: Micro-deletion in the Y chromosome frequency in France, averaged: 10–15% in cases of azoospermia, and 5–10% in cases of oligozoospermia.

Frequency:

Reference: (Aknin-Seifer et al., 2005)

Pubmed Link: PubMed

Male infertility

Genetics: Suggested that the POLG1 CAG-repeat polymorphisms does not contribute to oligozoospermia in French and Italian populations.

Frequency: 625 individuals in three groups of case-controls from three different Italian regions

Reference: (Brusco et al., 2006)

Pubmed Link: PubMed

Male infertility

Genetics: 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.

Frequency:

Reference: (Harris et al., 2006)

Pubmed Link: PubMed

Male infertility

Genetics: The mutated genotype was found at the same frequency in both infertile and normospermic Italian men.

Frequency:

Reference: (Krausz et al., 2004)

Pubmed Link: PubMed

Frequency study

Genetics: 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.

Frequency: The population sample consisted of 1,330 individuals from 3 large geographic areas: Europe, Southwest Asia, and Siberia/East Asia.

Reference: (Malyarchuk et al., 2005)

Pubmed Link: PubMed

Testicular cancer

Genetics: 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).

Frequency: 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.

Reference: (Nowak et al., 2005)

Pubmed Link: PubMed

Idiopathic sporadic Parkinson

Genetics: Increase frequency of non-10/11 (CAG) variant in Parkinson disease (PD)

Frequency: Luoma, 2007: found in 10% PD patients compared with 3.5-4.3% spouse/population controls.

Reference: (Luoma et al., 2007)

Pubmed Link: PubMed

Seminoma testicular cancer

Genetics: Homozygous lack of 10 CAG repeat

Frequency: 4.9% of Danish men (n=869). 96.7% of Seminoma pts.

Reference: (Jensen et al., 2008)

Pubmed Link: PubMed

Friedreich's Ataxia

Genetics: Age of onset of FRDA is inversely correlated to the POLG CAG repeats

Frequency: Study done in 49 Iranian FRDA pts.

Reference: (Heidari et al., 2008)

Pubmed Link: PubMed

Sporadic Parkinson

Genetics: 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.

Frequency: 243 Swedish PD patients and 279 Swedish controls

Reference: (Anvret, et al., 2010)

Pubmed Link: PubMed

PEO and ovarian failure

Genetics: Compound heterozygote found w/ K947R

Frequency:

Reference: (Baruffini et al., 2011)

Pubmed Link: PubMed

10/11Q

Genetics: 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.

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

Q43R 128 a→g (exon 2) Idiopathic sporadic Parkinson

Genetics:

Frequency:

Reference: (Luoma et al., 2007)

Pubmed Link: PubMed

Genetics: Reference # rs28567406

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=28567406

Pubmed Link: PubMed

Q44X 132 del gc (exon 2)

Genetics: Reference # rs35424491

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=35424491

Pubmed Link: PubMed

Q45R 134 a→g (exon 2) Epilepsy

Genetics: Found in trans w/ D136E

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Q49E 145 c→g (exon 2) Neutral polymorphism

Genetics:

Frequency: <1 % in control populations

Reference: (Luoma et al., 2007)

Pubmed Link: PubMed

Q49X 147 del gc (exon 2)

Genetics: Reference # rs72434227

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=72434227

Pubmed Link: PubMed

Q50X 149 del ag (exon 2)

Genetics: Reference # rs71879812

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=71879812

Pubmed Link: PubMed

Q53X 158 del aa (exon 2)

Genetics: Reference # rs41550117

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=41550117

Pubmed Link: PubMed

S64L 191 c→t (exon 2)

Genetics: Found in cis with R232H in ar Charcot-Marie-Tooth

Frequency: 30.6% of control population (90/294 control alleles)

Reference: (Harrower et al, 2008)

Pubmed Link: PubMed

Q68X 202 c→t (exon 2) Alpers

Genetics: Found in trans w/ A467T

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

L79F 235 c→t (exon 2) Epilepsy

Genetics: Found in compound with S1080I in an 8 yo female with adrenocortical insufficiency and hypothyroidy

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in compound with S1080I in an 8 yo female with epilepsy, cerebellar ataxia, and ptosis

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

L83P 248 t→c (exon 2) Alpers

Genetics: Compound heterozygous mutation with G888S in 10 yr. old

Frequency:

Reference: (Bao et al., 2008)

Pubmed Link: PubMed

Genetics:

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

F88L 264 c→g (exon 2)

Genetics: Found in trans w/ A467T in a 42 y.o. w/ no symptoms noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

H110Y 328 c→t (exon 2)

Genetics: Heterozygous, hypotonia, failure to thrive, short stature, respiratory failure

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

W113G 337 t→g (exon 2)

Genetics: Reference # rs77321104

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=77321104

Pubmed Link: PubMed

D136E 408 c→g (exon 2) Epilepsy

Genetics: Found in trans w/ Q45R

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

A143V 427 g→t (exon 2) Alpers

Genetics:

Frequency: Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA

Reference: (Sarzi et al. 2007)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ L304R in a 22 y.o. pt. with PEO and cerebral cavernous malformation.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ G848S in a 4 y.o. w/ hypotonia, encephalopathy, seizures, hepatic failure, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ G848S in a 38 y.o. w/ ataxia, peripheral neuropathy, hearing loss, and seizures

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in an 8 y.o. w/ seizures and an abnormal MRI

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ G848S in a 37 y.o. symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ A467T in a 49 y.o. w/ PEO, encephalopathy, ataxia, seizures, neuropathy, hearing loss, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

P163S 487 c→t (exon 2) Opthalmoplegia and seizures

Genetics: Found in trans w/T851A in a 21 y.o. female with peripheral neuropathy, seizures, dysarthria and bilateral ptosis

Frequency: 1 in 322 mitochondrial disease patients

Reference: (Woodbridge et al., 2012)

Pubmed Link: PubMed

E183X 547 del g (exon 2)

Genetics: Reference # rs35065786

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=35065786

Pubmed Link: PubMed

R193Q 578 g→a (exon 2) Neutral polymorphism

Genetics:

Frequency: 0.6% of 450 individuals

Reference: (GeneSNPs, 2004)

Pubmed Link: PubMed

Genetics: Reference # rs3176162

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=3176162

Pubmed Link: PubMed

C224Y 671 g→a (exon 3) Alpers

Genetics:

Frequency: Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA

Reference: (Sarzi et al. 2007)

Pubmed Link: PubMed

R227W 679 c→t (exon 3) PEO

Genetics: 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.

Frequency: 7 out of 27patients w/sporadic PEO compared to 250 controls individuals.

Reference: (Agostino et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Found as compound in trans w/ S1176L.  Also, found as compound in trans with T251I-P587L.

Frequency:

Reference: (Lamantea and Zeviani, 2004)

Pubmed Link: PubMed

Alpers, Severe childhood multi-system disorder

Genetics: In Alpers found as compound with A467T. In severe childhood multi-system disorder found as compound with D1184N

Frequency: 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

Reference: (de Vries et al., 2007)

Pubmed Link: PubMed

Myopathy and gastrointestinal obstruction

Genetics: Found in trans w/ G848S with mtDNA depletion and Cox deficient muscle fibers

Frequency:

Reference: (Giordano et al., 2009)

Pubmed Link: PubMed

R227P 680 g→c (exon 3) Severe childhood multi-system disorder

Genetics: Compound heterozygous with A467T

Frequency: 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

Reference: (de Vries et al., 2007)

Pubmed Link: PubMed

Epilepsy and failure to thrive

Genetics: Found in trans w/ A467T

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

R232G 694 c→g (exon 3) Infantile Hepatocerebral Syndrome

Genetics: Found as compound with T251I and P587L

Frequency: 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.

Reference: (Ferrari et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ [T251I and P587L]

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Hepatocerebral MDS

Genetics: Found in trans w/ [T251I andP587L]

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

R232H 695 g→a (exon 3) Liver failure, encephalopathy, and epilepsy

Genetics: Found as compound in trans with W748S - E1143G

Frequency: Not found in 200 control alleles

Reference: (Kollberg et al., 2006)

Pubmed Link: PubMed

Charcot-Marie Tooth disease, (CMT) (profound cerebellar ataxia)

Genetics: Found in cis with the S64L SNP and in trans with G737R

Frequency: Not detected in 282 control alleles

Reference: (Harrower et al, 2008)

Pubmed Link: PubMed

697 g→a (exon 3) Leigh Syndrome

Genetics: In trans w/G848S

Frequency:

Reference: (Taanman et al, 2008)

Pubmed Link: PubMed

695 g→a (exon 3) Infantile hepatocerebral

Genetics: Found in trans w/A467T and in cis w/H277L in a 2 mo. mold w/hypotonia, motor paresis and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

697 g→a (exon 3) Infantile hepatocerebral

Genetics: Found in trans w/A467T and in cis w/H277L in a 1.5 mo. old w/hypotonia and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Infantile hepatocerebral

Genetics: Found W748S and E1143G w/ A467T in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

Parkinsonism

Genetics: Found as a heterozygous mutation in a 25 yo male with sensorimotor neuropath, ataxia, and mtDNA deletions

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Sensorimotor neuropathy

Genetics: Found as a heterozygous mutation in a 30 yo female with axonal sensorimotor neuropathy

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Sensorimotor neuropathy

Genetics: Found as a heterozygous mutation in a 20 yo female with sensorimotor neuropath ,and ataxia

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

W235X 705 g→a (exon 3) Severe childhood multi-system disorder

Genetics: Found as compound heterozygote with A467T

Frequency: 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

Reference: (de Vries et al., 2007)

Pubmed Link: PubMed

Q238R 713 a→g (exon 3)

Genetics: Reference # rs56410699

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=56410699

Pubmed Link: PubMed

P241L 722 c→t (exon 3) Neutral polymorphism

Genetics:

Frequency: <1 % in control populations

Reference: (Luoma et al., 2007)

Pubmed Link: PubMed

Genetics: Found in a Chinese population with Parkinsonism at an allelic frequency of 0.326

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

L244P 731 t→c (exon 3) Infantile Hepatocerebral Syndrome

Genetics: Found as compound with W748S

Frequency: 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.

Reference: (Ferrari et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: Found 2 infants in trans with W748S

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

T251I 752 c→t (exon 3) PEO

Genetics: ar PEO. Found as compound with R309L, or 2354G insertion, or G848S in PEO. 

Frequency: 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. 

Reference: (Ferrari et al., 2005)

Pubmed Link: PubMed

PEO

Genetics: Found in compound with R807P

Frequency:

Reference: (Del Bo et al., 2003)

Pubmed Link: PubMed

Infantile Hepatocerebral Syndrome

Genetics: Frequently found in cis with P587L and compound in trans with L304R, V1106I, and R227W .

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency:

Reference: (Lamantea and Zeviani, 2004)

Pubmed Link: PubMed

PEO and mtDNA deletions

Genetics: 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.

Frequency: 31 mitochondrial myopathy patients without any family history for the disorder

Reference: (Di Fonzo et al., 2003)

Pubmed Link: PubMed

Infantile Hepatocerebral Syndrome

Genetics: 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.

Frequency: 7 out of 27patients w/sporadic PEO compared to 250 controls individuals.

Reference: (Agostino et al., 2003)

Pubmed Link: PubMed

MNGIE

Genetics: Found in cis with P587L and in trans w/N846S.

Frequency: Van Goethem, 2003: Not found in 280 control chromosomes

Reference: ( Van Goethem et al., 2003c) 

Pubmed Link: PubMed

Infantile Hepatocerebral Syndrome

Genetics: Found in 1 of 9 infantile hepatocerebral syndrome patients. In cis with P587L and compound with R232G.

Frequency: 9 infantile hepatocerebral patients of German and Italian descent.

Reference: (Ferrari et al., 2005)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency: 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population.

Reference: (Gonzalez - Vioque et al., 2006) 

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ G848S and in cis w/ P587L in a 75 y.o. male.

Frequency:

Reference: (Kollberg et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis w/ R232G and cis w/ P587L.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/ P587L, with both mutations on each allele. A 2nd pt. found to have P587L in trans and A467T in cis.

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

mtDNA depletion

Genetics: In cis w/P587L and in trans w/ E1136K

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Hepatocerebral MDS

Genetics: Found in cis with P587L and in trans with R232G

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

Restless leg syndrome, ptosis, diplopia, limb weakness, blurred vision

Genetics: Found in trans with P587L.

Frequency:

Reference: (Aitken, et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: Found in trans with W748S andP587L

Frequency:

Reference: (Tzoulis, et al., 2009)

Pubmed Link: PubMed

PEO and mental retardation

Genetics: Found in cis w/P587L and in trans w/ R275X

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

PEO, exercise intolerance, diabetes and a 2nd pt. w/ cataract and myopathy

Genetics: Found in cis w/P587L and in trans w/ A467T

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Ptosis

Genetics: Found in cis w/P587L and in trans w/ G848S

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Epilepsy and mental retardation

Genetics: ad, Found w/P587L

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Seizures, hypotonia, and developmental delay

Genetics: Found w/P587L

Frequency:

Reference: (Burusnukul and de los Reyes, 2009)

Pubmed Link: PubMed

Acute disseminated encephalomyelitis

Genetics: Found w/P587L, found in one 4 y.o. patient with autoimmune central nervous system disease

Frequency:

Reference: (Harris et al., 2010)

Pubmed Link: PubMed

SANDO

Genetics: Found sporadically w/P587L and G848S in a 80 y.o. male

Frequency:

Reference: (Wiess and Saneto, 2010)

Pubmed Link: PubMed

Ptosis and myopathy

Genetics: 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.

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/ P587L and in trans w/ H932Y in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Peripheral Neuropathy

Genetics: Found in cis w/ P587L and in trans w/ H932Y in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/ P587L and in trans w/ G848S in an 80 y.o. w/ peripheral neuropathy, ptosis, and abnormal muscle histology

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/ P587L and in trans w/ K1191N in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in cis w/ P587L and in trans w/ N1157S in a 9 y.o. Symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ G588D and in cis w/ P587L in a 6 y.o. w/ no symptoms noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in compound with G848S in a 45 yo female with mtDNA deletions

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

SANDO

Genetics: 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.

Frequency:

Reference: (Lovan et al., 2013)

Pubmed Link: PubMed

G268A 803 g→c (exon 3) PEO

Genetics: Sporadic / unknown Found as compound in trans with A467T

Frequency: Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians 

Reference: (Di Fonzo et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Sporadic / unknown Found as compound in trans with A467T

Frequency:

Reference: (Del Bo et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Sporadic / unknown Found as compound in trans with A467T

Frequency:

Reference: (Baruffini et al., 2006)

Pubmed Link: PubMed

PEO

Genetics: Sporadic / unknown Found as compound in trans with A467T

Frequency: 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population.

Reference: (Gonzalez - Vioque et al., 2006)

Pubmed Link: PubMed

Parkinsonism, dystonia, mental retardation, hepatocerebral syndrome, ptosis, neuropathy, and intestinal problems

Genetics: ar, 3 patients ages 3-16 yrs

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Genetics: Reference # rs61752784

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=61752784

Pubmed Link: PubMed

R275X 823 c→t (exon 3) PEO and mental retardation

Genetics: Found in trans w/ T251I+P587L

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

R275Q 824 g→a (exon 3) Multiple Sclerosis-like illness

Genetics: 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.

Frequency:

Reference: (Echaniz-Laguna et al., 2010)

Pubmed Link: PubMed

H277L 830 a→t (exon 3) Alpers

Genetics: Found in trans w/T851A

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Infantile hepatocerebral

Genetics: Found in trans w/A467T and in cis w/R232H in a 2 mo. old w/hypotonia, motor paresis and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Infantile hepatocerebral

Genetics: Found in trans w/A467T and in cis w/R232H in a 1.5 mo. old w/hypotonia and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Myelopathy,myopathy, peripheral neuropathy and subcortical grey matter degeneration

Genetics: Found in trans w/A862T in a 66 y.o. female with mtDNA deletions and subcortical grey matter degeneration

Frequency:

Reference: (McKelvie et al., 2012)

Pubmed Link: PubMed

Y282D 844 t→g (exon 3) Alpers

Genetics: Found in trans w/L304R in a patient with intractable convulsions and severe epileptic status.

Frequency: 1 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome

Reference: (Navarro-Sastre et al., 2012)

Pubmed Link: PubMed

G303R 907 a→g (exon 4) Encephalopathy

Genetics: Found in trans w/ A467T in 2 brothers and a 3rd unrelated pt. All 3 had ataxia, epilepsy, and encephalopathy.

Frequency: Not found in 170 control individuals

Reference: (Tzoulis, et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ A467T in a pediatric patient w/mitochondrial encelphalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

L304R 911 t→g (exon 4) PEO Ataxia - neuropathy

Genetics: ar  Compound in trans with A467T  Found as homozygous or compound in trans with W748S - E1143G in SCAE, ataxi-neuropathy

Frequency: Van Goethem et al., 2001 reported 0 out of 229 control Individuals (<0.4%)

Reference: (Van Goethem et al., 2001)

Pubmed Link: PubMed

PEO Ataxia - neuropathy

Genetics: ar  Compound in trans with A467T  Found as homozygous or compound in trans with W748S - E1143G in SCAE, ataxi-neuropathy

Frequency: Not found in 300 healthy French control chromosomes

Reference: (Naimi et al., 2006)

Pubmed Link: PubMed

PEO Ataxia - neuropathy

Genetics: ar  Compound in trans with A467T  Found as homozygous or compound in trans with W748S - E1143G in SCAE, ataxic-neuropathy

Frequency:

Reference: ( Stuart et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found homozygous in one pt.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ L392V and R1081dup.

Frequency:

Reference: (Cardenas et al., 2010)

Pubmed Link: PubMed

VPA induced liver toxicity

Genetics: Found in trans with A467T in a 15 y.o. pt. with VPA induced hepatotoxicity

Frequency: Used 968 alleles ethnically matched controls

Reference: (Stewart et al., 2010)

Pubmed Link: PubMed

Peripheral neuropathy

Genetics: Found as a homozygote in a 23 y.o. pt. with exercise intolerance, muscle weakness, and ragged red fibers.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ D1145GfsX9 in a developmentally delayed 12 y.o. with seizures and hypotonia.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ G737R in a 54 y.o. w/PEO, ptosis, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found as a homozygote in a 12 y.o. w/ PEO, ptosis, neuropathy, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found as a homozygote in a 9 y.o. with PEO, neuropathy, ptosis, and COX deficient fibers.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found as a homozygote in a 2 y.o. pt. w/ encephalopathy, seizures, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ A143V in a 22 y.o. pt. with PEO and cerebral cavernous malformation.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found as a homozygote in a 9 y.o. with ptosis, ataxia, hypotonia, and cerebellar atrophy.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found has a homozygote in a 4 y.o. w/ seizures, ptosis, and an abnormal MRI.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found as a homozygote in a 10 y.o. w/ ptosis, PEO, ataxia, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ A467T in a 15 y.o. symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ R1081dup in a 1 y.o. w/seizures and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ R1081P in a 10 y.o. w/ ataxia, seizures, PEO, and dystonia

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/G888D in a patient showing psychomotor retardation, epileptic encephalopathy, progressive cerebral atrophy, and altered liver enzymes.

Frequency: 2 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome

Reference: (Navarro-Sastre et al., 2012)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/Y282D in a patient with intractable convulsions and severe epileptic status.

Frequency: 2 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome

Reference: (Navarro-Sastre et al., 2012)

Pubmed Link: PubMed

SANDO

Genetics: Found as a homozygous mutation in a 15 yo male with 40% COX neg muscle fibers and multiple mtDNA deletions

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

PEO

Genetics: Found in compound with W748S in a 27 yo female with sensory and cerebellar ataxia, axonal sensory neuropathy

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

S305R 915 c→g (exon 4) Alpers

Genetics: heterozygous

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found as a compound heterozygote w/P1073L.

Frequency:

Reference: (Baruffini et al., 2011)

Pubmed Link: PubMed

Epilepsy and ataxia-neuropathy

Genetics: Heterozygous mutation w/R627Q found in a 5 y.o. pt. w/epilepsy at age 5, and developed ataxia and neuropathy in his teens.

Frequency:

Reference: (Baruffini et al., 2011)

Pubmed Link: PubMed

Liver Failure

Genetics: Found in trans w/ A467T in a 1 y.o. with liver failure

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 3 y.o. w/seizures and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Q308H 924 g→c (exon 4) PEO

Genetics: Found in trans w/W748S

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

R309L 926 g→t (exon 4) PEO

Genetics: ar, Compound with T251I

Frequency: Not found in 100 DNA samples

Reference: (Lamantea et al., 2002)

Pubmed Link: PubMed

R309H 926 g→a (exon 4) Alpers

Genetics: Compound in trans with R627Q

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

W312R 934 t→c (exon 4) PEO

Genetics: Found in a 39 y.o. with PEO as a heterozygous mutation

Frequency: 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG

Reference: (Agostino et al., 2003)

Pubmed Link: PubMed

Encephalopathy, dysphagia, and neuropathy

Genetics: Found in trans with R574W in a 62 y.o. male

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

K319E 955 a→g (exon 4) PEO

Genetics: Found in trans w/ R869Q in a 44 y.o. w/ PEO, ataxia, neuropathy, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

P324S 970 t→g (exon 4) Neutral polymorphism

Genetics:

Frequency: 0.6% of 450 individuals

Reference: (GeneSNPs, 2004)

Pubmed Link: PubMed

Genetics: Reference # rs2307437

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307437

Pubmed Link: PubMed

T326fs61X 975-976 ins c stop@387 (exon 4) Alpers

Genetics: Found in trans with A467T

Frequency: Not found in 300 healthy French control chromosomes

Reference: (Naimi et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found in compound with A467T in a 4 yo male with mtDNA depletion

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

S332X 994 del c or tc→g (exon 4)

Genetics: Reference # rs35954915

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=35954915

Pubmed Link: PubMed

W347_L356 del 1039-1068 del (exon 5) Alpers

Genetics: 10 amino acid del found in trans w/A467T

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

E358A 1073 a→c del364X (exon 4) Alpers

Genetics: Found in trans w/A467T in a 3 y.o. w/seizures, ataxia, and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

1073 a→c del364X (exon 4) Alpers

Genetics: Found in trans w/A467T in a 4 y.o. w/seizures, ataxia, and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

R374X 1120 c→t (STOP) (exon 5) Alpers

Genetics: Found in trans w/A467T.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

G380D 1139 g→a (exon 5) PEO

Genetics: Sporadic mutation found in trans with A467T

Frequency: Not found in 300 healthy French control chromosomes

Reference: (Naimi et al., 2006)

Pubmed Link: PubMed

PEO

Genetics: Found in compound with A467T in a 63 yo male with cerebellar ataxia, weakness of lower limbs and cognitive impairment

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

R386C 1156 c→t (exon 5) Isolated distal myopathy of upper limbs and mtDNA depletion

Genetics: Found as a compound heterozygote w/ H932Y in one 27 y.o. male. Recessive inheritance of both mutated alleles confirmed.

Frequency:

Reference: (Giordano et al., 2010)

Pubmed Link: PubMed

R386H 1157 g→a (exon 5) Alpers

Genetics: Heterozygous single mutation found in a 1 y.o..

Frequency:

Reference: (Baruffini et al., 2011)

Pubmed Link: PubMed

L392V 1174 c→g (exon 6) Neutral polymorphism

Genetics: Heterozygous with muscle weakness & optic atrophy

Frequency: <1 % in control populations

Reference: (Luoma et al., 2007) (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis w/R1081dup and in trans w/L304R

Frequency:

Reference: (Cardenas et al., 2010)

Pubmed Link: PubMed

L392W 1174 ct→tg (exon 6)

Genetics: Found in a Chinese population with Parkinsonism at an allelic frequency of 0.199

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

R417T 1250 g→c (exon 6&7 junction) Alpers

Genetics: Found in trans w/A467T

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Exon 7 deletion c.1251-2 a→t (exon 6&7 splice site) Alpers

Genetics: Found as a compound heterozygote with A467T. The pt. was a 3.5 y.o. male with VPA induced liver toxicity.

Frequency:

Reference: (Schaller et al., 2011)

Pubmed Link: PubMed

C418R 1252 t→c (exon 7) Alpers

Genetics: Found in trans w/A467T.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 43 mo. old female with ataxia and seizures

Frequency:

Reference: (McCoy et al., 2011)

Pubmed Link: PubMed

L424GfsX28 1270-1271 del ct stop @ 452 (exon 7) PEO

Genetics: Sporadic / unknown Compound with G431V

Frequency: 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG

Reference: (Agostino et al., 2003)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with A467T

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

G426S 1276 g→a (exon 7) Epilepsy, ataxia, myoclonus, cataract, and cognitive delay

Genetics: ar, found in a 56 yr. old pt. with 2 siblings with epilepsy

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ G737R in an 11 y.o. w/ seizures and an abnormal MRI

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

L428P 1283 t→c (exon 7) Alpers

Genetics: Found as a heterozygote w/ A467T.

Frequency: 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.

Reference: (Sarzi et al. 2007)

Pubmed Link: PubMed

M430L 1288 a→t (exon 7) PEO with Parkinsonism

Genetics: ar, Compound (in trans) heterozygous with W918R

Frequency: Absent in 200 control alleles

Reference: (Invernizzi et al., 2008)

Pubmed Link: PubMed

PEO

Genetics: Found in trans with W918R in a 42 y.o. male with PEO and mtDNA deletions

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

G431V 1292 g→t (exon 7) PEO

Genetics: Sporadic / unknown Compound with L424 CT deletion

Frequency: 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG

Reference: (Agostino et al., 2003)

Pubmed Link: PubMed

S433C 1298 c→g (exon 7) PEO- ataxia, peripheral neuropathy

Genetics: 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.

Frequency: Hudson, 2006: Not detected in 200 controls

Reference: (Hudson et al., 2006a)

Pubmed Link: PubMed

PEO

Genetics: Sporadic, Found in trans with E1143G

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Q449X 1345 c→t (exon 7) Alpers

Genetics: Found in trans w/ W748S in a 21 y.o. with seizures

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Y452X 1356 t→g (exon 7) PEO

Genetics: Sporadic

Frequency: Not detected in 200 controls.

Reference: (Hudson et al., 2006a)

Pubmed Link: PubMed

Multiple Sclerosis-like illness

Genetics: 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.

Frequency:

Reference: (Echaniz-Laguna et al., 2010)

Pubmed Link: PubMed

L463F 1389 g→t (exon 7) PEO

Genetics: ar, Found as compound in trans with S511N

Frequency: None found in 192 ethnically matched control chromosomes nor in 108 patients with PEO and 140 cases of sporadic PD

Reference: (Hudson et al., 2006b)

Pubmed Link: PubMed

M464T 1391 t→c (exon 7) neuropathy and ataxia

Genetics: Found in compound with K768E in a teenage female with axonal sensorimotor neuropathy and sensory ataxia with multiple mtDNA deletions

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

A467T 1399 g→a (exon 7) PEO

Genetics: Found as compound with L304R and R3P in PEO.  Also found as a homozygous mutation in a PEO pt.

Frequency: Three out of 229 control individuals were heterozygous for A467T (allele T frequency 0.6%), while the R3P and L304R mutations were not observed.

Reference: (Van Goethem et al., 2001)

Pubmed Link: PubMed

PEO

Genetics: Found as compound with S1104C in a 48 y.o. pt. with PEO 

Frequency: 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG

Reference: (Agostino et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Found in compound with G268A

Frequency: Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians 

Reference: (Di Fonzo et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Found as compound with R627Q, L304R or R3P, or G268A  

Frequency: Van Goethem, 2003: absent in 612 Belgian controls.

Reference: (Van Goethem et al., 2003a)

Pubmed Link: PubMed

MERRF

Genetics: homozygous mutation in an 18 y.o. patient w/ myoclonus, seizure, and sensory ataxic neuropathy

Frequency:

Reference: (Van Goethem et al., 2003b)

Pubmed Link: PubMed

Alpers

Genetics: Found in compound het with E873stop in Alpers w/ mtDNA depletion

Frequency:

Reference: (Naviaux and Nguyen, 2004)

Pubmed Link: PubMed

Neurodegenerative disorders and ataxia

Genetics: 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.

Frequency:

Reference: (Van Goethem et al., 2004)

Pubmed Link: PubMed

Genetics:

Frequency:

Reference: (Chan et al., 2005a)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency:

Reference: (Chan et al., 2005b)

Pubmed Link: PubMed

Infantile Hepatocerebral Syndrome

Genetics: 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.

Frequency: 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.

Reference: ( Ferrari et al., 2005)

Pubmed Link: PubMed

ataxia-myopathy syndrome

Genetics: Found as a heterozygous mutation in 4 family members, and found in compound with R627Q in a 5th family member.

Frequency:

Reference: ( Luoma et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency:

Reference: (Nguyen et al., 2005)

Pubmed Link: PubMed

Ataxia Syndrome

Genetics: Found as a homozygous mutation in 2 members of the same family with mtDNA deletions

Frequency:

Reference: (Winterthun et al., 2005)

Pubmed Link: PubMed

PEO

Genetics: Found as a homozygous mutation in a 33 y.o. male with mtDNA deletions

Frequency: 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population.

Reference: (Gonzalez-Vioque et al., 2006)

Pubmed Link: PubMed

Encephalopathy, liver disorders, and PEO

Genetics: 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.

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Oxidative phosphorylation enzyme complex deficiencies

Genetics: Found as a homozygous mutation in 1 of 8 patients. Also found in trans w/ R227W, R227P, W235X, G848S, and A957P.

Frequency: 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

Reference: (de Vries et al., 2007)

Pubmed Link: PubMed

Liver failure, encephalopathy, and epilepsy

Genetics: Found in trans w/ R574W, G848S, W748S in children w/ progressive encephalopathy.

Frequency: Not found in 200 control alleles

Reference: (Kollberg et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ T914P, T326fsX38, and G380D

Frequency: Not found in 300 healthy French control chromosomes

Reference: (Naimi et al., 2006)

Pubmed Link: PubMed

Epilepsy, PEO, and ataxia

Genetics: Found as a homozygous mutation in 5 mitochondrial disease pts. Also, found in trans w/W748S in 6 pts. with mitochondrial disease.

Frequency: Studied in 26 mitochondrial disease patients

Reference: (Tzoulis et al., 2006)

Pubmed Link: PubMed

PEO

Genetics: Identified a diverse range of phenotypes arising from PEO-associated amino acid substitutions introduced in the yeast pol gamma gene.

Frequency:

Reference: (Stuart et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found as a heterozygote mutation with L428P.

Frequency: 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.

Reference: (Sarzi et al., 2007)

Pubmed Link: PubMed

Alpers w/ valporate induced hepatic failure

Genetics: Found in cis w/T885s and in trans w/Q879H and E1143G.

Frequency:

Reference: (McFarland et al., 2008)

Pubmed Link: PubMed

Alpers, Ataxia Neuropathy, and arPEO+

Genetics: Found in trans w/ L886P, Q68X, Q715X, T849H, T914P, L83P, G888S, R1138C, c.2480+1, c. 2157+5, G737R, and L424G

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Alpers, PEO

Genetics: 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.

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/T914P

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ R574W

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Homozygous

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ splice variant c.3643 +2t>c

Frequency:

Reference: (Roels, et al., 2009)

Pubmed Link: PubMed

mtDNA depletion

Genetics: Found in trans w/ G8484S.

Frequency:

Reference: (Roels, et al., 2009)

Pubmed Link: PubMed

Prematurity, epilepsy, deafness, retinitis pigmentosa, hemiparesis, and liver failure

Genetics: Found in trans w/ K925RfsX42

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: 5 patients found with a homozygous mutation

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Epilepsy and failure to thrive

Genetics: Found in trans w/ R227P

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

PEO, exercise intolerance, diabetes, and a 2nd pt. w/ cataract and myopathy

Genetics: 2 patients; found in trans w/ T251I + P587L

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/S305R

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

PEO, ptosis, polyneuropathy, ataxia, and dysarthria

Genetics: Found in trans w/ W748S and in compound w/ E1143G

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Epilepsy, myoclonus, polyneuropathy, ataxia, and cognitive delay; a 2nd pt. with epilepsy and MELAS-like symptoms

Genetics: Found in trans w/ W748S

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Epilepsy, myoclonus, and developmental delay

Genetics: Found in trans w/T914P

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Epilepsy, liver failure, occipital strokes, and growth retardation

Genetics: Found in trans w/ A957P

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Spinocerebellar ataxia, neuro-degeneration, and impaired cognitive functions

Genetics: ar, 2 patients ages 19 and 48

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Epilepsy and myoclonus

Genetics: ar, found with E1143G

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia

Genetics: Found with W748S in a 43 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, sensory neuropathy, and dysphagia

Genetics: Homozygous. Found in 2 early 20 yr. old sisters, and only one with epilepsy

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

SANDO

Genetics: Homozygous. Found in 2 siblings in their mid 40's. mtDNA deletions and COX1 deficient fibers in muscle biopsies

Frequency:

Reference: (McHugh et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with G848S

Frequency:

Reference: (Hasselmann et al., 2009)

Pubmed Link: PubMed

Hepatocerebral - Alpers symptoms

Genetics: Found in trans w/P1073L in 2 pt., Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility.

Frequency:

Reference: (Kurt et al., 2010)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in trans w/ G303R in 2 brothers and a 3rd unrelated pt. All 3 had ataxia, epilepsy, and encephalopathy.

Frequency: Not found in 170 control individuals

Reference: (Tzoulis et al., 2010)

Pubmed Link: PubMed

SANDO

Genetics: Found in trans with W748S+E1143G. Sensory ataxia, dysarthria, and opthalmoplegia.

Frequency:

Reference: (Posada et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Compton et al., 2010 and Tang et al., 2011)

Pubmed Link: PubMed

Multiple Sclerosis-like illness

Genetics: 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.

Frequency:

Reference: (Echaniz-Laguna et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ P625R in a 1 y.o. with epilepsy and liver failure.

Frequency:

Reference: (Baruffini et al., 2011)

Pubmed Link: PubMed

Epilepsy

Genetics: Found heterozygous with T 914P in a 10 mo. old male with myoclonic seizures and jerks, and developmental regression.

Frequency:

Reference: (Dhamija et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with E1143G, Q497H and W748S in a 6 y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with T914P in a 9 mo. old with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

VPA induced liver toxicity

Genetics: Found in trans with L304R in a 15 y.o. pt. with VPA induced hepatotoxicity

Frequency: Used 968 alleles ethnically matched controls

Reference: (Stewart et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: 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

Frequency:

Reference: (Schaller et al., 2011)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in trans with Q715X in a 5 y.o. pt.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Liver Diseases

Genetics: Compound heterozygote in cis with W748S

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ T914P in a 3 y.o. with hypotonia, encephalopathy, seizures, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ G848S in an 8 y.o. pt. with seizures, muscle weakness, hypotonia, ataxia, hearing loss, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ G848S in a 1 y.o. pt. with seizures and elevated transaminases, and increased signal basal ganglia

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

SANDO AND PEO

Genetics: Found in trans w/ W748S in a 54 y.o. with PEO, ptosis, ataxia, neuropathy, and SANDO

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ W748S in a 16 y.o. with seizures, dystonia, choria, neuropathy, and ptosis

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Encephalopathy and ataxia

Genetics: Found in trans w/ R597W in a 26 y.o. with encephalopathy, ataxis, ptosis, and neuropathy

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/K1050RfsX44 in a 4 y.o. w/ seizures, ataxia, hypotonia, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found as a homozygote in a 46 y.o. pt. w/ ptosis, neuropathy, muscle weakness, and ataxia

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/W748S in an 18 y.o. with ataxia, seizures, dystonia, and optic atrophy.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Ataxia

Genetics: Found as a homozygote in a 48 y.o. w/ hypotonia, ataxia muscle weakness, and headaches.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in a 2 y.o. w/ hypotonia, encephalopathy, seizures, cardiomyopathy, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found as a homozygote in a 19 y.o. w/ ataxia, myoclonic seizures, optic atrophy, dysarthria, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO and seizures

Genetics: Found as a homozygote in a 40 y.o. w/ PEO, ataxia, seizures, and neuropathy

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ L1113P in a 1 y.o. with encephalopathy, seizures, and hepatic failure

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ T914P in a 5 y.o. w/ seizures, hearing loss, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Liver failure

Genetics: Found in trans w/ S305R in a 1 y.o. with liver failure

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures and liver failure

Genetics: Found in trans w/ R852C and G11D in a 8 mo. w/ seizures, liver failure, and lactic acidosis.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ F749S in a 6 y.o. w/ seizures

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Hepatic failure

Genetics: Found in trans w/ S1095R in a 6 mo. w/ hypotonia, liver failure, abnormal muscle histology, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ T914P in a 9 mo. w/ seizures, hypotonia, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures and hepatic failure

Genetics: Found in trans w/ T914P in a 4 y.o. with liver failure, seizures, and failure to thrive

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ Q1024X in a 2y.o. w/seizures, hearing loss, and hemiparesis

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ W748S in a 29 y.o. symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ A143V in a 49 y.o. w/ PEO, encephalopathy, ataxia, seizures, neuropathy, hearing loss, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ L304R in a 15 y.o. Symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Liver failure

Genetics: Found in trans w/ R807C in a 1 y.o. w/ encephalopathy, liver failure, and lactic acidosis

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ T914P in an 8 mo. w/ seizures, respiratory failure, and an abnormal MRI

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ F749S in an 8 mo. symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures and hepatic failure

Genetics: Found in trans w/ H754Q in a 2 y.o. w/ seizures, hepatic failure, and cerebellar atrophy.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ C1188R in a 3 y.o. w/ seizures, hypotonia, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

VPA induced liver failure

Genetics: Found in trans w/ G588D in a 2 y.o. w/ VPA induced liver failure

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ F88L in a 42 y.o. w/ no symptoms noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/G848S in a 3 y.o. w/seizures, developmentally delayed, and ataxia

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/G848S in a 11 mo. old w/seizures and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found as a homozygous mutation in a 10 y.o. w/seizures and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/IVS14+1G>A in a 2 y.o. w/seizures, developmentally delayed, and ataxia

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/R852C in a 5 y.o. w/seizures, ataxia, and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/S305R in a 3 y.o. w/seizures and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/L966R in a 1 y.o. w/ seizures and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/E358A del364X in a 3 y.o. w/seizures, ataxia, and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/E358A del364X in a 4 y.o. w/seizures, ataxia, and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/L966R in a 1 y.o. w/ seizures and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Infantile hepatocerebral

Genetics: Found in trans w/R232H and H277L in a 2 mo. old w/hypotonia, motor paresis and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Infantile hepatocerebral

Genetics: Found in trans w/R232H and H277L in a 1.5 mo. old w/hypotonia and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ R574W in 2 pediatric patients w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ G848S in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ G303R in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/L966R in a 17 mo. old male with seizures and encephalopathy

Frequency:

Reference: (McCoy et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency:

Reference: (McCoy et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/R852C in a 21 mo. old female with blindness, anarthria, hypotonia, and epilepsy

Frequency:

Reference: (McCoy et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/C418R in a 43 mo. old female with ataxia and seizures

Frequency:

Reference: (McCoy et al., 2011)

Pubmed Link: PubMed

Alpers to Leigh's encephalopathy

Genetics: Found in trans w/G848S in a 3.5 mo. old female with seizures and Alpers. Post mortem studies revealed Leigh's encephalopathy

Frequency:

Reference: (Scalais et al., 2012)

Pubmed Link: PubMed

MNGIE-like

Genetics: Found as a homozygous mutation in a 46 y.o. male with PEO, ptosis, exercise intolerance, peripheral neuropathy, ataxia, and hearing loss

Frequency:

Reference: (Tang et al., 2012)

Pubmed Link: PubMed

Torticollis and PEO

Genetics: Found in trans w/W748S in a 43 y.o. female with abnormal gait, ataxia, PEO, and head jerks.

Frequency:

Reference: (Tuladhar et al., 2012)

Pubmed Link: PubMed

Parieto-occipital lobe epilepsy

Genetics: Found in trans w/ W748S in a 16 y.o. female with seizures, headaches, cerebellar ataxia, axonal neuropathy, visual impairment, and impaired cognitive function

Frequency:

Reference: (Roshal et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/W748S in a 24 y.o. female with arPEO, cerebellar ataxia, and mtDNA deletions

Frequency:

Reference: (Lax et al., 2012b)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/X1240Q in a 59 y.o. male with arPEO and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012b)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/X1240Q in a 59 y.o. male with arPEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/X1240Y in a 42 y.o. Female with arPEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found as a homozygous mutation in a 36 y.o. male with arPEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/W748S in a 47 y.o. male with arPEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/X1240Y in a 42 y.o. female with PEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found as a homozygous mutation in a 44 y.o. male with arPEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/W748S in a 48 y.o. male with PEO, ptosis, ataxia and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in trans w/W748S in a 18 y.o. female with epilepsy, ataxia and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in trans w/W748S in a 20 y.o.female with epilepsy, ataxia and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

Genetics: Found in a Chinese population with Parkinsonism at an allelic frequency of 0.028

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

PEO

Genetics: Found in compound with G380D in a 63 yo male with cerebellar ataxia, weakness of lower limbs and cognitive impairment

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Alpers

Genetics: Found in compound with T326fs61X in a 4 yo male with mtDNA depletion

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Alpers

Genetics: Found in compound withT914P in a 15 month female with mtDNA depletion

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in compound withW748S in a 17 yo female with axonal neuropathy, cerebellar ataxia, and hyperintensity of rolandic,

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Sensorimotor neuropathy

Genetics: Found as a heterozygous mutation in a 60 yo with ALS-like symptoms and mtDNA deletions.

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found as a homozygous mutation in 2 teens both had epilepsy, ataxia, and PEO

Frequency:

Reference: (Tzoulis et al., 2013)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found as a heterozygous mutation with W748S in 2 patients with PEO and ataxia.

Frequency:

Reference: (Tzoulis et al., 2013)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found as a heterozygous mutation with G848S in a patient with epilepsy

Frequency:

Reference: (Tzoulis et al., 2013)

Pubmed Link: PubMed

SANDO

Genetics: 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.

Frequency:

Reference: (Lovan et al., 2013)

Pubmed Link: PubMed

Epilepsy

Genetics: 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.

Frequency:

Reference: (Sitarz et al., 2014)

Pubmed Link: PubMed

MIRAS

Genetics: 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.

Frequency:

Reference: (Sitarz et al., 2014)

Pubmed Link: PubMed

N468D 1402 a→g (exon 7) PEO

Genetics: Found in compound w/A1105T in a family w/PEO

Frequency: Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes.

Reference: (Luoma et al., 2004)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/A1105T in 3 family members w/ PEO

Frequency:

Reference: (Wanrooij et al., 2004)

Pubmed Link: PubMed

Microcephaly, cerebellar atrophy, hypotonia, and retinitis pigmentosa

Genetics: Found as a heterozygous mutation in a 15 y.o. female w/ progressive cerebellar atrophy, hypotonia, and retinitis pigmentosa.

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Sensory neuropathy and PEO

Genetics: 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

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Opthmalplegia and peripheral neuropathy

Genetics: Found in trans w/T851A in a 49 y.o. female with ptosis, lower limb weakness, sensory ataxia, gastrointestinal symptoms, and peripheral neuropathy

Frequency: 1 in 322 mitochondrial disease patients

Reference: (Woodbridge et al., 2012)

Pubmed Link: PubMed

c. 1433 +1g→a 1433 ins g→a (Splice variant between ex 7 and ex 8) Seizures

Genetics: Found in trans w/ A467T in a 2 y.o. w/ hypotonia, encephalopathy, seizures, cardiomyopathy, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Y479X 1433 large del (exon 8)

Genetics: Reference # rs71653298

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=71653298

Pubmed Link: PubMed

Q497H 1491 g→c (exon 8) Ataxia Syndrome

Genetics: Found allelic (cis) with W748S + E1143G

Frequency: 1 in 97 found in healthy controls and 1 in 99 found mtDNA disease patients

Reference: (Winterthun et al., 2005)

Pubmed Link: PubMed

Alpers, Ataxia Neuropathy

Genetics: In cis with W748S-E1143G. Also found in trans w/G848S, and also in trans w/A467T.

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: In cis w/ W748S and E1143G, and in trans w/ G848S.

Frequency: Found in one child w/ a normal brain MRI

Reference: (Brunetti-Pierri et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with E1143G and W748S, and in trans with A467T in a 6 y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

S511N 1532 g→a (exon 8) PEO

Genetics: ad

Frequency: None found in 192 ethnically matched control chromosomes nor in 108 patients with PEO and 140 cases of sporadic PD

Reference: (Hudson et al., 2006b)

Pubmed Link: PubMed

K512M 1535 a→t (exon 8) Parkinsonism

Genetics: Found as a heterozygous mutation in a 79 yo male with PEO and parkinsonism

Frequency:

Reference: (Dulhon et al., 2013)

Pubmed Link: PubMed

G517V 1550 g→t (exon 8) Ataxia - neuropathy

Genetics: Found in trans w/ E1143G in a father and his 8 y.o. daughter w/ exercise intolerance, ataxia, and neuropathy.

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Leigh Syndrome

Genetics: Found as a heterozygous mutation in a female pt. w/ dominant ataxia and neuropathy

Frequency: 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.

Reference: (Sarzi et al., 2007)

Pubmed Link: PubMed

Myopathy and micro-cephaly

Genetics: Found in trans w/ D1196N and R1128H

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

adPEO

Genetics: Heterozygous, short-stature, Leigh-like disease, neuropathy, stroke, dystonia, chorea, diabetes, myoclonus, Sideroblastic anemia, splenomegaly, Pearson Syndrome to KSS

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Myoclonic epilepsy

Genetics: In trans w/R722H, and in association w/ a mutation in SCN1A, R1645Q

Frequency:

Reference: (Bolszak et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, dystonia, epilepsy, PEO, hypotonia, mental retardation, and chorea

Genetics: ad, 4 patients ages 4-40 yrs.

Frequency: <0.5% in a Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Seizures, hypoglycemia, myoclonus, hypotonia, and developmental delay

Genetics: Heterozygous, found in 2 half siblings and their unaffected mother

Frequency:

Reference: (Burusnukul and de los Reyes, 2009)

Pubmed Link: PubMed

Cerebellar ataxia, PEO, and dysphagia

Genetics: Heterozygous. Found in a 44 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Diabetes, strokes, psychosis, and epilepsy

Genetics: Heterozygous. Ad, found in twins, their mother, and grandmother

Frequency:

Reference: (Hopkins et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: 56 y.o. male with a heterozygous mutation, and ptosis, myopathy, neuropathy, and mtDNA deletions.

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found as a heterozygous mutation in a 33 y.o. female with PEO and mtDNA deletions. Father also affected.

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/ Y955C in a 47 y.o. w/ PEO, ptosis, myopathy, and neuropathy

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures and mitochondrial myopathy

Genetics: Found as a heterozygous mutation in a 56 y.o. woman with mitochondrial myopathy, seizures, ataxia, dysarthria, and dysphonia

Frequency: 1 in 322 mitochondrial disease patients

Reference: (Woodbridge et al., 2012)

Pubmed Link: PubMed

Neuronal ceroid lipofuscinosis

Genetics: 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.

Frequency:

Reference: (Staropoli et al., 2012)

Pubmed Link: PubMed

Neutral polymorphism

Genetics: Biochmeical analysis of the recombinant Pol gamma with G517V revealed wild type activity

Frequency:

Reference: (Kasiviswanathan and Copeland, 2011)

Pubmed Link: PubMed

R546C 1636 c→t (exon 9) Neutral polymorphism

Genetics: 1%

Frequency: 1.1% of 450 individuals

Reference: (GeneSNPs, 2004)

Pubmed Link: PubMed

Genetics: Heterozygous with R628Q in one breast tumor

Frequency:

Reference: (Singh et al, 2009)

Pubmed Link: PubMed

Genetics: Reference # rs2307447

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307447

Pubmed Link: PubMed

R546S 1636 c→a (exon 9)

Genetics: Reference # rs2307447

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307447

Pubmed Link: PubMed

R546G 1636 c→g (exon 9)

Genetics: Reference # rs2307447

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307447

Pubmed Link: PubMed

K561M 1882 a→t (exon 9) Dysmorphy, hypotonia, coloboma, heart failure, and liver insufficiency

Genetics: Compound heterozygosity in cis with W748S

Frequency: 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.

Reference: (Sarzi et al., 2007)

Pubmed Link: PubMed

R562Q 1685 g→a (exon 9) PEO

Genetics: sporadic

Frequency: Not found in 100 DNA samples from healthy Italians

Reference: (Di Fonzo et al., 2003)

Pubmed Link: PubMed

H569Q 1707 c→(a or g) (exon 9)

Genetics: Homozygous

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

R574W 1720 c→t (exon 10) PEO

Genetics: Found in trans w/ W312R in a 37 y.o. male patient w/ PEO, dysphagia, and myopathy.

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Liver failure, encephalopathy, and epilepsy

Genetics: Found in trans w/A467T in 2 family members whose parent are unaffected heterozygotes.

Frequency: Kollberg, 2006: Not found in 200 control alleles

Reference: (Kollberg et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ A467T

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ A467T in 2 pediatric patients w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

R579W 1735 c→t (exon 10) PEO

Genetics: Sporadic / unknown Compound with A889T

Frequency: Not detected in 120 healthy control alleles

Reference: (Filosto et al., 2003)

Pubmed Link: PubMed

W585X 1754 g→a (exon 10) PEO

Genetics: Found in trans with P648R in a 50 y.o. male with PEO, dysphagia, dysphonia, and parkinsonism with mtDNA deletions

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

P587L 1760 c→t (exon 10) PEO, neuropathy, and hearing loss

Genetics: Found in trans w/ Q1236H in 2 different families and affected siblings

Frequency: Filosto, 2003: not detected in 120 healthy control alleles. 

Reference: (Filosto et al., 2003) 

Pubmed Link: PubMed

PEO and mtDNA deletions

Genetics: 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.

Frequency: Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians.

Reference: (Di Fonzo et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Found in compound w/T251I and N864S in 2 sisters.

Frequency: Van Goethem, 2003: Not found in 280 control chromosomes.

Reference: (Van Goethem et al., 2003c)

Pubmed Link: PubMed

Infantile Hepatocerebral Syndrome

Genetics: Found in compound w/T251I and R232G

Frequency: 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.

Reference: (Ferrari et al., 2005)

Pubmed Link: PubMed

PEO

Genetics: Found in compound w/T251I and G8484S in a 75 y.o. male

Frequency:    

Reference: (Kollberg et al., 2005)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency:

Reference: (Lamantea and Zeviani, 2004) 

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/T251I and trans w/M603L. Also found in trans w/ R853W (no T251I). All had mtDNA deletions.

Frequency: 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population.

Reference: (Gonzalez-Vioque et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis w/ T251I and in trans w/ G848S, also found as a hetero. mutation with ataxia, ptosis, and neuropathy

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/R232G and in cis w/T251I. Also, in cis w/P589L and in trans w/W748S.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with T251I with both mutations on each allele. Also, found in cis w/A467T and in trans w/T251I.

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

mtDNA depletion

Genetics: In cis w/T251I and in trans w/E1136K

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Hepatocerebral MDS

Genetics: Found in cis w/ T251I and in trans w/ R232G

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

Restless leg syndrome, ptosis, diplopia, limb weakness, blurred vision

Genetics: Found in trans with T251I.

Frequency:

Reference: (Aitken, et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: Found in cis with W748S and in trans with T251I.

Frequency:

Reference: (Tzoulis, et al., 2009)

Pubmed Link: PubMed

PEO and mental retardation

Genetics: Found in cis w/ T251I and in trans w/ R275X

Frequency: >0.5% of Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

PEO, exercise intolerance, diabetes and a 2nd pt. w/ cataract and myopathy

Genetics: Found in cis w/T251I and in trans w/A467T

Frequency: >0.5% of Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Ptosis

Genetics: Found in cis w/T251I and in trans w/G848S

Frequency: >0.5% of Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

PEO, ptosis, epilepsy, mental retardation, ataxia, polyneuropathy, and cataract

Genetics: 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

Frequency: >0.5% of Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Seizures, hypotonia, and developmental delay

Genetics: Found w/T251I

Frequency:

Reference: (Burusnukul and de los Reyes, 2009)

Pubmed Link: PubMed

Acute disseminated encephalomyelitis

Genetics: Found w/T251I, found in one 4 yr. old patient with autoimmune central nervous system disease

Frequency:

Reference: (Harris et al., 2010)

Pubmed Link: PubMed

SANDO

Genetics: Found sporadically w/T251I and G848S in a 80 yr. old male

Frequency:

Reference: (Weiss and Saneto, 2010)

Pubmed Link: PubMed

Ptosis and myopathy

Genetics: 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.

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/ T251I and in trans w/ H932Y in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Peripheral Neuropathy

Genetics: Found in cis w/ T251I and in trans w/ H932Y in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/ T251I and in trans w/ G848S in an 80 y.o. w/ peripheral neuropathy, ptosis, and abnormal muscle histology.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/ T251I and in trans w/ K1191N in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in cis w/ T251I and in trans w/ N1157S in a 9 y.o. Symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ G588D and in cis w/ T251I in a 6 y.o. w/ no symptoms noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

SANDO

Genetics: 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.

Frequency:

Reference: (Lovan et al., 2013)

Pubmed Link: PubMed

G588D 1763 g→a (exon 10) VPA induced liver failure

Genetics: Found in trans w/ A467T in a 2 y.o. w/ VPA induced liver failure

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ T251I and P587L in a 6 y.o. w/ no symptoms noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

P589L 1766 c→t (exon 10) Alpers

Genetics: Found in cis w/P587L and in trans w/W748S.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

L591F 1774c→t (exon 10) SANDO

Genetics: Found in trans w/R1096C in a 48 y.o. female with SANDO and dysphagia.

Frequency:

Reference: (Kurt et al., 2012)

Pubmed Link: PubMed

R597W 1789 c→t (exon 10) PEO with ataxia

Genetics: Homozygous

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

PEO, seizures, and VPA induced liver failure

Genetics: Found as a homozygote in an 18 y.o. with PEO, neuropathy, seizures, and VPA induced hepatotoxicity

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Encephalopathy and ataxia

Genetics: Found in trans w/ A467T in a 26 y.o. w/ encephalopathy, ataxia, neuropathy, and ptosis.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

M603L 1807 a→t (exon 10) PEO with ptosis

Genetics: Found as compound in trans with T251I-P587L

Frequency: 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population.

Reference: (Gonzalez-Vioque et al., 2006)

Pubmed Link: PubMed

L605R 1814_1815 tt→gc (exon 10) Alpers

Genetics: Found in trans w/ A467T. Mitochondria depletion in liver

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

Y614X 1842 c→ a or g

Genetics: Reference # rs62640033

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640033

Pubmed Link: PubMed

R617C 1849 c→t (exon 10)

Genetics: Heterozygous with muscle weakness, exercise intolerance, hearing loss, arrhythmia

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

L623W 1868 t→g (exon 10) Hypoketotic, hypyoglycaemial, and liver dysfunction

Genetics: Compound heterozygote w/ K755E

Frequency: Not found in 200 healthy controls

Reference: (Bortot, et al., 2009)

Pubmed Link: PubMed

P625R 1874 c→g (exon 10) Alpers

Genetics: Found as a compound heterozygote w/ A467T in a 1 y.o. with epilepsy and liver failure.

Frequency:

Reference: (Baruffini et al., 2011)

Pubmed Link: PubMed

R627W 1879 c→t (exon 10) PEO

Genetics: Found in trans w/A467T in a 39 y.o. male whose unaffected parents are hets for each mutation.

Frequency: Van Goethem, 2003: absent in 612 Belgian controls.

Reference: (Van Goethem et al., 2003a) 

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ A467T in 2 PEO patients w/ hearing loss

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/T914P

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in compound with W748S in teenage sisters with epilepsy, encephalitis with mitochondrial abnormalities affecting neurons

Frequency:

Reference: (Nolte et al., 2013)

Pubmed Link: PubMed

R627Q 1880 g→a (exon 10) Ataxia - myopathy  PEO - ataxia - neuropathy Alpers 

Genetics: 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

Frequency:

Reference: (Luoma et al., 2005)

Pubmed Link: PubMed

Ataxia - myopathy  PEO - ataxia - neuropathy Alpers 

Genetics: 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

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

MELAS

Genetics: Found w/ G848S; heterozygous mutation; w/ mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

Frequency:

Reference: (Deschauer et al., 2007)

Pubmed Link: PubMed

Ataxia Neuropathy

Genetics: Found in cis w/ G11D and in trans w/ R852C.

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia

Genetics: Found with G848S in a 35 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia

Genetics: Found with T1199X ins. a at c.3594 in a 47 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia

Genetics: Found with R1096C in a 43 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Epilepsy and ataxia-neuropathy

Genetics: Found as a compound heterozygote w/S305R in a 5 y.o. with epilepsy that developed ataxia and neuropathy in his teens.

Frequency:

Reference: (Baruffini et al., 2011)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in trans w/ R852C and G11D in a 25 y.o. w/ dementia, encephalopathy, and stroke.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R628Q 1883 g→a (exon 10)

Genetics: Mutation found in one breast tumor heterozygous w/ the SNP R546C

Frequency:

Reference: (Singh et al., 2009)

Pubmed Link: PubMed

P648R 1943 c→g (exon 10) SANDO

Genetics: Found in compound w/R807C in a 39 y.o. patient.

Frequency:

Reference: (Gago et al., 2006)

Pubmed Link: PubMed

PEO + myopathy

Genetics: ar, Found as either homozygous mutation or as compound in trans with R1096C in PEO.

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Ptosis and myopathy

Genetics: 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.

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

SANDO

Genetics: Found in trans with R807C in a 49 y.o. pt. with SANDO and mtDNA deletions

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans with W585X in a 50 y.o. male with PEO, dysphagia, dysphonia, and parkinsonism with mtDNA deletions

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

H659Q 1977 c→g (exon 11)

Genetics: Reference # rs62640030

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640030

Pubmed Link: PubMed

E662K 1984 g→a (exon 11) Neutral polymorphism

Genetics:

Frequency: 2.8% of 450 individuals

Reference: (GeneSNPs, 2004)

Pubmed Link: PubMed

Q666L 1997 a→t (exon 11)

Genetics: Reference # rs62640029

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640029

Pubmed Link: PubMed

R709X 2125 c→t (exon 12) PEO

Genetics: Found as compound with T251I.

Frequency:

Reference: (Del Bo et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Found as compound with T251I-P587L in a pt. w/ mtDNA deletions.

Frequency: Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians

Reference: (Di Fonzo et al., 2003)

Pubmed Link: PubMed

Q715X 2143 c→t (exon 12) Alpers

Genetics: Found in trans w/ A467T

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in trans w/ A467T in a 5 y.o. pt.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

c.2157+5_+6gc>ag 2157 gc→ ag (exon 12) Alpers

Genetics: Found in trans with A467T, most likely a splice site mutation.

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

R722H 2165 g→a (exon 13) Neutral polymorphism

Genetics:

Frequency: <1 % in control populations

Reference: (Luoma et al., 2007)

Pubmed Link: PubMed

Myoclonic epilepsy

Genetics:

Frequency:

Reference: (Bolszak et al., 2009)

Pubmed Link: PubMed

PEO, mtDNA deletions and neurological phenotypes

Genetics: 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

Frequency: 1:135 carrier frequency in a Finnish population

Reference: (Komulainen et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with V1044A in a 2.5 y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Genetics: Found in a Chinese population with Parkinsonism at an allelic frequency of 0.033

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

H734R 2201 a→g (exon 13)

Genetics: Reference # rs56119329

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=56119329

Pubmed Link: PubMed

N736S 2207 a→g (exon 13) Ataxia, cardiomyopathy, and depression

Genetics: Found in a 52 y.o. female with melancholic depression, unstable gailt, and dilated cardiomyopathy.

Frequency:

Reference: (Verhoeven et al., 2011)

Pubmed Link: PubMed

G737R 2209 g→c (exon 13) Epilepsy and liver failure

Genetics: Found as compound in trans with A767D in two family members

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006) 

Pubmed Link: PubMed

Parkinsonism

Genetics: Parkinsonism in trans with R853W.

Frequency:

Reference: (Davidzon et al., 2006)

Pubmed Link: PubMed

2210 g→c (exon 13) Charcot-Marie Tooth disease, (CMT) (profound cerebellar ataxia)

Genetics: Found in trans with the S64L-R232H in CMT.

Frequency: Found in 2/666 (0.3%) of control alleles

Reference: (Harrower et al, 2008)

Pubmed Link: PubMed

arPEO+ and Myocerebrohepatopathy (MCHS)

Genetics: Found in trans w/ A467T. In trans w/ E1143G-R943C in MCHS.  Also, found as a single heterozygous mutation.

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

PEO

Genetics: Found in trans with W748S.

Frequency:

Reference: (Tzoulis, et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ L304R in a 54 y.o. with PEO, ptosis, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ G426S in an 11 y.o. w/ seizures and an abnormal MRI

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ V855L in an 8 mo. w/ seizures, liver failure, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans A957V in a 4 mo. No symptoms noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Epilepsy

Genetics: 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.

Frequency:

Reference: (Sitarz et al., 2014)

Pubmed Link: PubMed

N740D 2218 a→g (exon 13)

Genetics: Reference # rs78347903

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=78347903

Pubmed Link: PubMed

V742M 2224 g→a (exon 13) SNP

Genetics: Reference # rs147827654

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusID=5428

Pubmed Link: PubMed

G746S 2236 g→a (exon 13) Ataxia, PEO

Genetics: ar, Found in cis w/ E1143G, and in trans G848S

Frequency: 1in 454 alleles

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/G848S in a 36 y.o. male with PEO, peripheral neuropathy, and ataxia

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

W748S 2243 g→c (exon 13) Ataxia

Genetics: Found in compound w/E1143G w/ataxia, dysarthria, and cognitive impairment. Also found as a homozygous mutation.

Frequency:

Reference: (Van Goethem et al., 2004) 

Pubmed Link: PubMed

Infantile Hepatocerebral Syndrome

Genetics: Found in trans w/ Y1210fs1216X and also in trans w/ L244P

Frequency: 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.

Reference: (Ferrari et al., 2005)

Pubmed Link: PubMed

Hepatocerebral Syndrome

Genetics: Found in 4 children in cis w/E1143G and in trans w/G8484S.

Frequency:

Reference: (Davidzon et al., 2005)

Pubmed Link: PubMed

Ataxia

Genetics: Found as a homozygous mutation w/ E1143G

Frequency: Carrier frequency in the general Finnish population of 1:125 from 500 control chromosomes

Reference: (Hakonen et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/E1143G and in cis w/G848S in a 13 mo. old male

Frequency:

Reference: (Nguyen et al., 2005)

Pubmed Link: PubMed

Ataxia Syndrome

Genetics: Found in trans w/Q497H in patients w/ progressive ataxia and epilepsy

Frequency: 1 in 97 found in healthy controls and 1 in 99 found mtDNA disease patients

Reference: (Winterthun et al., 2005) 

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/A467T and also in trans w/ Q308H

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

SCAE

Genetics: Found in trans w/L304R in a 20 y.o. female w/ spinocerebellar ataxia epilepsy syndrome and mtDNA deletions

Frequency: Not found in 300 healthy French control chromosomes

Reference: (Naimi et al., 2006)

Pubmed Link: PubMed

PEO, ataxia, and epilepsy

Genetics: 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.

Frequency: Studied in 26 mitochondrial disease patients

Reference: (Tzoulis et al., 2006)

Pubmed Link: PubMed

Ataxia Neuropathy

Genetics: 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

Frequency:

Reference: (Chan et al., 2006) 

Pubmed Link: PubMed

Alpers

Genetics: Found in cis w/K561M and found in cis with E1143G. Both patients had mtDNA depletion

Frequency: 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.

Reference: (Sarzi, et al. 2007)

Pubmed Link: PubMed

Alpers, Ataxia Neuropathy, and arPEO+

Genetics: Found in trans w/ G848S, and in cis w/ Q479H-E1143G. Also found in trans w/ A467T. arPEO+ as a compound w/ E1143G

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Homozygous, juvenile onset

Frequency:

Reference: (Uusimaa et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: 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].

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

PEO and Alpers

Genetics: Found in trans w/ A467T. In a 2nd pt., found in cis w/ E1143G and in trans w/ G11D and R852C.

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: In cis w/E1143G and in trans w/ G484S

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

mtDNA depletion

Genetics: In cis w/E1143G and in trans w/ H1110Y and Q1236H

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: In cis w/ Q497H and E1143G, and in trans w/ G848S

Frequency: Found in one child w/ a normal brain MRI

Reference: (Brunetti-Pierri et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in 2 infants in trans w/ Y1210X

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ L244P

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ D930N

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

Parkinsonism

Genetics: Homozygous mutation w/ PEO, ataxia, peripheral neuropathy, and hearing loss

Frequency:

Reference: (Remes et al., 2009)

Pubmed Link: PubMed

Leigh Syndrome

Genetics: Found in trans with G11D and R852C

Frequency:

Reference: (Naess, et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: Found in trans with G737R, and in a 2nd pt. in cis with P587L and in trans with T251I.

Frequency:

Reference: (Tzoulis, et al., 2009)

Pubmed Link: PubMed

PEO, ptosis, polyneuropathy, ataxia, and dysartria

Genetics: Found in trans w/A467T and in compound w/ E1143G

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Epilepsy, myoclonus, polyneuropathy, ataxia, and cognitive delay; a 2nd pt. with epilepsy and MELAS-like symptoms

Genetics: Found in trans w/ A467T.

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia

Genetics: Found with A467T in 4 middle aged patients, 2 of which are sisters

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia

Genetics: Homozygous in a 39 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Hepatocerebral - Alpers symptoms

Genetics: Found w/P1073L. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility

Frequency:

Reference: (Kurt et al., 2010)

Pubmed Link: PubMed

SANDO

Genetics: Found in trans w/ P1073L. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility

Frequency:

Reference: (Posada et al., 2010)

Pubmed Link: PubMed

PEO, mtDNA deletions and neurological phenotypes

Genetics: Found in trans with A467T and in cis with E1143G. Sensory ataxia, dysarthria, and opthalmoplegia.

Frequency: 1:135 carrier frequency in a Finnish population

Reference: (Komulainen et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: 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

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with E1143G and in trans with R807C in a 1 y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with E1143G and Q497H, and in trans with A467T in a 6 y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with E1143G and in trans with G848S in a 11 mo. old with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with 1143G and in trans with T914P in a 2.5 y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Ataxia and cerebellar atrophy

Genetics: Found as a homozygote in a 30 y.o. pt. with peripheral neuropathy, ataxia, and fatigability

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

SANDO and PEO

Genetics: Found in trans w/ A467T in a 54 y.o. with PEO, ptosis, ataxia, neuropathy, and SANDO

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in a 16 y.o. with seizures, dystonia, choria, neuropathy, and ptosis

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: 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

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ D892fsX39 in a 9 mo. old pt. w/ a deceased sibling

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ G848S in a 5 y.o. pt. w/myclonic seizures, liver failure, and hypotonia

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ Q449X in a 21 y.o. with seizures

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ G848S in a 7 y.o. w/ seizures and cortical blindness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ G848S in a 3 y.o.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: 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.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/A467T in an 18 y.o. with ataxia, seizures, dystonia, and optic atrophy.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ R953C in a 51 y.o. w/ peripheral neuropathy, ptosis, hypotonia, ataxia, and seizures.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ T914P in a 5 y.o. w/ seizures

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ T914P in an 8 mo. w/ seizures, hypotonia, abnormal MRI, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ A467T in a 29 y.o. symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures and liver failure

Genetics: Found in trans w/ M797del in a 1 y.o. with seizures and hepatic failure

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures and liver failure

Genetics: Found in trans w/ G888D in a 2 y.o. w/ seizures, hepatic failure, ketosis and abnormal MRI

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ R852H in a 3 y.o. w/ Alpers

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

MSCAE

Genetics: Found in trans w/ T914P in a 15 y.o. female with mitochondrial spinocerebellar ataxia and epilepsy.

Frequency:

Reference: (Hinnell et al., 2012)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/G848S in a 6 yr. 4 mo. with microvesicular fatty changes of the liver, myclonic seizures, and ataxia

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: found in trans w/G8484S in a 6 yr. 9 mo. with seizures, developmentally delayed, and ataxia.

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found w/ E1143G and R232H in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

Alpers

Genetics: Found w/M1163R and E1143G in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

MNGIE-like

Genetics: Found in a 25 y.o. female as a homozygous mutation. Patient had migraines, ptosis, PEO, exercise intolerance, peripheral neuropathy, and ataxia.

Frequency:

Reference: (Tang et al., 2012)

Pubmed Link: PubMed

MNGIE-like

Genetics: Found in compound with R953C in a 50y.o. male with cognitive impairment, muscle weakness, diarrhea, vomiting, ptosis, and opthalmoparesis.

Frequency:

Reference: (Tang et al., 2012)

Pubmed Link: PubMed

Alpers and PEO

Genetics: Found in trans with R852C in a pediatric female patient with hypotonia, developmental delay, ataxia, and seizures

Frequency:

Reference: (Vasta et al., 2012)

Pubmed Link: PubMed

MIRAS

Genetics: 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.

Frequency: Frequencies in Europe for W748S+E1143G or A467T range from 0.6% in Belgium, 0.8% in Finland, and 2% in Finland

Reference: (Palin et al., 2012)

Pubmed Link: PubMed

Torticollis and PEO

Genetics: Found in trans w/A467T in a 43 y.o. female with abnormal gait, ataxia, PEO, and head jerks.

Frequency:

Reference: (Tuladhar et al., 2012)

Pubmed Link: PubMed

Parieto-occipital lobe epilepsy

Genetics: Found in trans w/ A467T in a 16 y.o. female with seizures, headaches, cerebellar ataxia, axonal neuropathy, visual impairment, and impaired cognitive function

Frequency:

Reference: (Roshal et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/A467T in a 24 y.o. female with arPEO, cerebellar ataxia, and mtDNA deletions

Frequency:

Reference: (Lax et al., 2012b)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ R1096C in a 49 y.o. male with PEO, ptosis, epilepsy and peripheral neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ A467T in a 47 y.o. male with arPEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/A467T in a 48 y.o. male with PEO, ptosis, ataxia and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in trans w/A467T in a 18 y.o.female male with epilepsy, ataxia and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in trans w/A467T in a 20 y.o. female male with epilepsy, ataxia and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

Genetics: Found in a Chinese population with Parkinsonism at an allelic frequency of 0.391

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in compound with R627W in teenage sisters with epilepsy, encephalitis with mitochondrial abnormalities affecting neurons

Frequency:

Reference: (Nolte et al., 2013)

Pubmed Link: PubMed

PEO

Genetics: Found in compound with L304R in a 27 yo female with sensory and cerebellar ataxia, axonal sensory neuropathy

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in compound with A467T in a 17 yo female with axonal neuropathy, cerebellar ataxia, and hyperintensity of rolandic,

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in compound with T914P in a 6 yo male with epilepsy and hepatic cholestasis and cytolysis, and mtDNA deletions

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

SANDO

Genetics: Found as a homzygous mutation in a 37 yo male with SANDO, parkinsonism, and mtDNA deletions

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Epilepsy

Genetics: Found as a heterozygous mutation in a 2 yo female with epilepsy, delayed psychomotor development, and mtDNA deletions and depletion.

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found as a heterozygous mutation with A467T in 2 patients with PEO and ataxia.

Frequency:

Reference: (Tzoulis et al., 2013)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found as a homozygous mutation in 7 patients with ataxia, epilepsy, and PEO

Frequency:

Reference: (Tzoulis et al., 2013)

Pubmed Link: PubMed

Epilepsy

Genetics: 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.

Frequency:

Reference: (Sitarz et al., 2014)

Pubmed Link: PubMed

MIRAS

Genetics: 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.

Frequency:

Reference: (Sitarz et al., 2014)

Pubmed Link: PubMed

MIRAS

Genetics: 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

Frequency:

Reference: (Sitarz et al., 2014)

Pubmed Link: PubMed

F749S 2246 t→c (exon 13) Alpers

Genetics: Found in compound with A467T

Frequency: Not found in 300 control chromosomes

Reference: (Nguyen et al., 2006)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ c.3104 +3a→t in a 66 y.o. w/ PEO, ptosis, myopathy, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in a 6 y.o. w/ seizures

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ A467T in an 8 mo. symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Optic atrophy

Genetics: Found in trans w/c.3104+3A>T in a 65 y.o. male with ptosis, dysphagia, exercise induced myalgia, limb weakness, and diabetes.

Frequency:

Reference: (Milone et al., 2011)

Pubmed Link: PubMed

L752P 2255 t→c (exon 13) Epilepsy, seizures, VPA induced liver failure

Genetics: Found in trans w/W748S and E1143G

Frequency:

Reference: (Zsurka, et al., 2008)

Pubmed Link: PubMed

H754Q 2262 c→g (exon 13) Seizures and hepatic failure

Genetics: Found in trans w/ A467T in 2 y.o. w/ seizures, hepatic failure, cerebellar atrophy, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

K755E 2263 g→a (exon 13) Hypoketotic, hypyoglycaemial, and liver dysfunction

Genetics: Compound heterozygote w/ L623W

Frequency: Not found in 200 healthy controls

Reference: (Bortot, et al., 2009)

Pubmed Link: PubMed

G763R 2287 g→c (exon 14) PEO, SANDO

Genetics: ar, Found as a homozygous mutation in PEO-SANDO

Frequency: Not found in 500 ethnically-matched control chromosomes

Reference: (Santoro et al., 2006)

Pubmed Link: PubMed

P765T 2293 c→a (exon 14) Ataxia neuropathy spectrum and gastroparesis

Genetics: Found as a homozygous mutation in a 52 y.o. woman with ptosis, ataxia neuropathy, gastroparesis, and opthalmoplegia

Frequency:

Reference: (Bostan et al., 2012)

Pubmed Link: PubMed

A767D 2300 c→a (exon 14) Alpers

Genetics: Found as compound in trans with G737R

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Epilepsy

Genetics: 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.

Frequency:

Reference: (Sitarz et al., 2014)

Pubmed Link: PubMed

K768E 2302 a→g (exon 14) neuropathy and ataxia

Genetics: Found in compound with M464T in a teenage female with axonal sensorimotor neuropathy and sensory ataxia with multiple mtDNA deletions

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

G785fs21X 2354 ins g stop @ 806 (exon 14) PEO

Genetics: ar, Compound with T251I

Frequency: Absent in 100 control DNA samples

Reference: (Lamantea et al., 2002)

Pubmed Link: PubMed

R790H 2369 g→a (exon 14) SNP

Genetics: Reference # rs191490663

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusID=5428

Pubmed Link: PubMed

M797del 2391-2393 gat de (exon 14) Seizures and liver failure

Genetics: Found in trans w/ W748S in a 1 y.o. with seizures and hepatic failure

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

A804T 2410 g→a (exon 14) Fatigue, muscle complaints, and bulbar dysarthria

Genetics: ar, found in one 55 yr. old pt.

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

R807H 2420 g→a (exon 14) Seizures and hepatic failure

Genetics: Found in trans w/ A467T in a 1 y.o. with seizures, hepatic failure, hypotonia, and failure to thrive

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R807P 2420 g→c (exon 14) PEO

Genetics: Sporadic Compound with T251I

Frequency:

Reference: (Del Bo et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Found in compound w/T251I/ P587L in1 pt. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions.

Frequency: Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians

Reference: (Di Fonzo et al., 2003)

Pubmed Link: PubMed

R807C 2419 c→t (exon 14) SANDO

Genetics: Found in compound w/P648R in a 39 y.o. patient.

Frequency:

Reference: (Gago et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with E1143G and W748S in a 1 y.o. with epilepsy and Encephalopathy

Frequency:

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Ptosis and myopathy

Genetics: Found as a heterozygous mutation in a 74 y.o. male with myopathy, ptosis, and diplopia

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

SANDO

Genetics: Found in trans with P648R in a 49 y.o. pt. with SANDO and mtDNA deletions.

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

Liver failure

Genetics: Found in trans w/ A467T in a 1 y.o. w/ encephalopathy, liver failure, and lactic acidosis

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: 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

Genetics: 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.

Frequency:

Reference: (Compton et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found as a compound heterozygote w/ A467T in a 3.5 y.o. The father carried the A467T mutation, and the mother the deletion.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al. 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 2 y.o. w/seizures, developmentally delayed, and ataxia

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

c. 2480+1g>a 2480+1 g→a splice site (exon 15) Alpers

Genetics: Found in trans w/ W748S-E1143G

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

IVS15-9- c.2485del 12bp 2485 del 12bp (exon 16) Alpers

Genetics: Splice site mutation 3'exon15/intron junction, Found in trans with A467T

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

IVS16-10 c>t IVS16-10 c>t (exon 16) Cerebellar ataxia, sensory neuropathy, and dysphagia

Genetics: Homozygous. Found in a 60 y.o. patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Y831F 2492 a→t (exon 16)

Genetics: Reference # rs41549716

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=41549716

Pubmed Link: PubMed

Y831S 2492 a→c (exon 16)

Genetics: Reference # rs41549716

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=41549716

Pubmed Link: PubMed

Y831C 2492 a→g (exon 16) Epilepsy, exericise intolerance, and hearing loss

Genetics: 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.

Frequency: Analysis by mispairing PCR showed the pres- ence of mutation Y831C in 57% of 87 controls.

Reference: (Barthelemy et al., 2002)

Pubmed Link: PubMed

PEO, neuropathy, and parkinsonism

Genetics: 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.

Frequency: Mancuso 2004: Not seen in 120 control subjects 

Reference: (Mancuso et al., 2004b) 

Pubmed Link: PubMed

Genetics: 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.

Frequency: Stopinska 2006: present in the Polish population at a frequency of 2.25%. 

Reference: (Stopinska et al., 2006)

Pubmed Link: PubMed

Neutral polymorphism

Genetics: 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.

Frequency: Tiangyou 2006: Found at the same frequency in age-matched controls. 

Reference: (Tiangyou et al., 2006)

Pubmed Link: PubMed

Neutral polymorphism

Genetics: 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.

Frequency: The coding region of POLG1 was analyzed in 140 Finnish patients with PD and their 127 spouses as age- and ethnically matched controls.

Reference: (Luoma et al., 2007)

Pubmed Link: PubMed

Genetics: Heterozygous, hypotonia, Autism, neuropathy, ataxia, hearing loss, short stature, muscle weakness, fatigue

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

mtDNA depletion

Genetics: In trans w/ H1134R

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

mtDNA deletions and seizures

Genetics: Heterozygous mutation found in a 34 y.o. woman with seizures, opthalmoparesis, ptosis,, peripheral neuropathy…..

Frequency: 2 in 322 mitochondrial disease patients

Reference: (Woodbridge et al., 2012)

Pubmed Link: PubMed

Muscle weakness

Genetics: Heterozygous mutation found in a 46 y.o. woman with proximal weakness and myagia, and muscle twitches.

Frequency: 2 in 322 mitochondrial disease patients

Reference: (Woodbridge et al., 2012)

Pubmed Link: PubMed

Genetics: Found in a Chinese population with Parkinsonism at an allelic frequency of 0.034

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

G848S 2542 g→a (exon 16) PEO

Genetics: Compound with T251I

Frequency: Lamantea, 2002: absent in 100 control DNA samples

Reference: (Lamantea et al., 2002) 

Pubmed Link: PubMed

Alpers

Genetics: Found in compound w/A467T in a 6 mo. male w/

Frequency: 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.

Reference: (Ferrari et al., 2005) 

Pubmed Link: PubMed

Alpers

Genetics: Found as compound W748S/E1143G.

Frequency:

Reference: (Davidzon et al., 2005)

Pubmed Link: PubMed

PEO

Genetics: Compound with T251I and P587L in a 75 y.o. male 

Frequency:

Reference: (Kollberg et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: Found as compound in Alpers with A467T and also in trans w/ W748 /E1143G.

Frequency:

Reference: (Nguyen et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: Found as compound in Alpers with A467T in a 6 mo. female

Frequency: 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

Reference: (de Vries et al., 2007)

Pubmed Link: PubMed

Alpers

Genetics: Found as compound with A467T in a 6 mo. female w/ liver failure and encephalopathy

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Liver failure, encephalopathy, and epilepsy

Genetics: Found as compound with A467T in a 3 mo. male w/ liver failure and encephalopathy

Frequency: Not found in 200 control alleles

Reference:   (Kollberg et al., 2006)

Pubmed Link: PubMed

MELAS

Genetics: Found w/ R627Q; heterozygous mutation; w/ mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

Frequency:

Reference: (Deschauer et al., 2007)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with A467T, Q497H, W748S, and E1143G. Also found in trans w/ T251I-P587L.

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/W748S, and in a 2nd pt. in trans w/A467T.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

PEO and Ataxia

Genetics: In trans w/ G746S and E1143G. Also found in trans w/ A467T.

Frequency: Found in one child with a normal brain MRI.

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

Leigh Syndrome

Genetics: In trans w/R232H

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: In trans w/E1143G +W748S

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ Q497H, W748S, and E1143G.

Frequency:

Reference: (Brunetti-Pierri et al., 2008)

Pubmed Link: PubMed

Myopathy and gastrointestinal obstruction

Genetics: Found in trans w/ R227W with mtDNA depletion and Cox deficient muscle fibers

Frequency:

Reference: (Giordano et al., 2009)

Pubmed Link: PubMed

mtDNA depletion

Genetics: Found in trans with A467T

Frequency:

Reference: (Roels, et al., 2009)

Pubmed Link: PubMed

Ptosis

Genetics: ar, found in trans w/ T251I+P587L

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia

Genetics: Found with R627Q in a 35 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with A467T

Frequency:

Reference: (Hasselmann et al., 2009)

Pubmed Link: PubMed

Hepatocerebral - Alpers symptoms

Genetics: Found in trans w/P1073L. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility

Frequency:

Reference: (Kurt et al., 2010)

Pubmed Link: PubMed

SANDO

Genetics: Found sporadically w/T251I and P587L in a 80 yr. old male

Frequency:

Reference: (Weiss and Saneto, 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with W748S and E1143G in a 11 mo. old with epilepsy and encephalopathy

Frequency:

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Liver Diseases

Genetics: Found in trans w/A467T in a 2 y.o. pt.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in an 8 y.o. pt. with seizures, muscle weakness, hypotonia, ataxia, hearing loss, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in a 1 y.o. with seizures, elevated transaminases, and increased signal basal ganglia

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ W748S in a 5 y.o. pt. w/myclonic seizures, liver failure, and hypotonia

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ W748S in a 7 y.o. w/ seizures and cortical blindness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ W748S in a 3 y.o.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: 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.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found as a homozygote in a 5 y.o. with seizures, an abnormal MRI, and abnormal respiratory enzymes.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in trans w/ R1096C in a 2 y.o. w/ hypotonia, ptosis, hepatic failure, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Failure to thrive

Genetics: Found in trans w/ P1073L in a 2 y.o. w/ hypotonia, and gastro-esophageal reflux.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ T25IL and P587L in an 80 y.o. w/ ptosis, PEO, peripheral neuropathy, and abnormal muscle histology.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A143V in a 4 y.o. w/ hypotonia, encephalopathy, seizures, hepatic failure, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A143V in a 38 y.o. w/ ataxia, peripheral neuropathy, hearing loss, and seizures

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ c.3104+3a→t in a 63 y.o. w/ PEO, ptosis, hearing loss, muscle weakness and ragged red fibers

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A143V in an 8 y.o. w/ seizures and an abnormal MRI

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ A143V in a 37 y.o. symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/W748S in a 6 yr. 4 mo. with micro-vesicular fatty changes of the liver, myclonic seizures, and ataxia

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: found in trans w/W7484S in a 6 yr. 9 mo. with seizures, developmentally delayed, and ataxia.

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 3 y.o. w/seizures, developmentally delayed, and ataxia

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 11 mo. old w/seizures and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ A467T in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency:

Reference: (McCoy et al., 2011)

Pubmed Link: PubMed

Alpers and Leigh's encephalopathy

Genetics: Found in trans w/A467T in a 3.5 mo. old female with seizures and Alpers. Post mortem studies revealed Leigh's encephalopathy

Frequency:

Reference: (Scalais et al., 2012)

Pubmed Link: PubMed

Optic atrophy

Genetics: Also found in w/ c.3104+3A>T in a 63 y.o. male with exercise intolerance, hearing loss, ptosis, and parkinsonism.

Frequency:

Reference: (Milone et al., 2011)

Pubmed Link: PubMed

Parkinsonism

Genetics: Found in trans w/S1104C in a 59 y.o. male with mtDNA deletions and cerebellar ataxia

Frequency:

Reference: (Lax et al., 2012b)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/G746S in a 36 y.o. male with PEO, peripheral neuropathy, and ataxia

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found in compound with T251I in a 45 yo female with mtDNA deletions

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found as a heterozygous mutation with A467T in a patient with epilepsy

Frequency:

Reference: (Tzoulis et al., 2013)

Pubmed Link: PubMed

T849H 2544 (insertion of c with fs868X) (exon 16) Alpers

Genetics: Found in trans with A467T and in cis with Q1236H

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

T851A 2551 a→g (exon 16) Alpers

Genetics: Found in trans w/R1047W.

Frequency: Not found in over 100 control alleles

Reference: (Wiltshire et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/H277L.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Opthmalplegia and seizures

Genetics: Found in trans w/P163S in a 21 y.o. female with peripheral neuropathy, seizures, dysarthria and bilateral ptosis

Frequency: 2 in 322 mitochondrial disease patients

Reference: (Woodbridge et al., 2012)

Pubmed Link: PubMed

Opthmalplegia and peripheral neuropathy

Genetics: Found in trans w/N468D in a 49 y.o. female with ptosis, lower limb weakness, sensory ataxia, gastrointestinal symptoms, and peripheral neuropathy

Frequency: 2 in 322 mitochondrial disease patients

Reference: (Woodbridge et al., 2012)

Pubmed Link: PubMed

R852C 2554 c→t (exon 16) Alpers

Genetics: Compound with A467T

Frequency: Not found in 300 control chromosomes

Reference: (Nguyen et al., 2006)

Pubmed Link: PubMed

Ataxia Neuropathy

Genetics: Found in trans w/ G11D-R627Q

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

Leigh Syndrome

Genetics: Found in cis with G11D and in trans with W748S

Frequency:

Reference: (Naess, et al., 2009)

Pubmed Link: PubMed

Multiple system atrophy

Genetics: Found with G11D in a 58 y.o. female with progressive cerebellar atrophy. Pt. had mtDNA deletions and mtDNA depletion.

Frequency:

Reference: (Mehta et al., 2011)

Pubmed Link: PubMed

Seizures and liver failure

Genetics: Found in trans w/ A467T and in cis w/ G11D in a 8 mo. w/ seizures, liver failure, and lactic acidosis.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in cis w/ G11D and in trans w/ R627Q in a 25 y.o. w/ dementia, encephalopathy, and stroke.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 5 y.o. w/seizures, ataxia, and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 21 mo. old female with blindness, anarthria, hypotonia, and epilepsy

Frequency:

Reference: (McCoy et al., 2011)

Pubmed Link: PubMed

Alpers and PEO

Genetics: Found in trans with W748S in a pediatric female patient with hypotonia, developmental delay, ataxia, and seizures

Frequency:

Reference: (Vasta et al., 2012)

Pubmed Link: PubMed

R852H 2555 g→a (exon 16) Alpers

Genetics: Found in trans w/ W748S in a 3 y.o. w/ Alpers

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R853W 2557 c→t (exon 16) PEO with ptosis

Genetics: Found as compound in trans with P587L Parkinsonism in compound in trans with G737R

Frequency: 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population.

Reference: (Gonzalez - Vioque et al., 2006)

Pubmed Link: PubMed

Parkinsonism

Genetics:

Frequency:

Reference: (Davidzon et al., 2006)

Pubmed Link: PubMed

R853Q 2558 g→a (exon 16) Myocerebrohepatopathy

Genetics: In trans with T251I-P587L

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

V855L 2563 g→t (exon 16) Seizures

Genetics: Found in trans w/ G737R in an 8 mo. w/ seizures, liver failure, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

V855A 2564 t→c (exon 16)

Genetics: Heterozygous with muscle weakness.

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

A862T 2584 g→a (exon 16) Ataxia Neuropathy

Genetics: Compound heterozygous with R964C

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

PEO with ataxia

Genetics: In trans w/R1047W

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, neuropathy, epilepsy, and restless leg syndrome

Genetics: Found heterozygous with R964C in 2 siblings that died in their early 20's

Frequency:

Reference: (Stricker et al., 2009)

Pubmed Link: PubMed

Alpers-like

Genetics: Found in trans with R1081Q in a 7 y.o. male with Alpers-like symptoms. Affected sibling.

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

Alpers-like

Genetics: Found in trans with R1081Q in a 4 y.o. male with Alpers-like symptoms. Affected sibling.

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

Myelopathy,myopathy, peripheral neuropathy and subcortical grey matter degeneration

Genetics: Found in trans w/H277L in a 66 y.o. female with mtDNA deletions and subcortical grey matter degeneration

Frequency:

Reference: (McKelvie et al., 2012)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ R1047W in a 61 y.o. female with PEO, ptosis, peripheral neuropathy, ataxia, and dysarthria.

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

N864S 2591 a→g (exon 16) PEO

Genetics: Found as compound with T251I-P587L

Frequency: Not found in 280 control chromosomes

Reference: (Van Goethem et al., 2003c)

Pubmed Link: PubMed

IVS16-10 c>t IVS16-10 c>t (exon 16) Cerebellar ataxia, sensory neuropathy, and dysphagia

Genetics: Homozygous. Found in a 60 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

R869Q 2606 g→a (exon 17) Myopathy w/ neurogenic atrophy; sensomotor axonal polyneuropathy, ataxia, and ptosis

Genetics: Autosomal recessive, found in a 32 yr. old pt.

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ K319E in a 44 y.o. w/ PEO, ataxia, neuropathy, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

E873X 2617 g→t (exon 17) Alpers

Genetics: Found in trans with A467T and under goes nonsense-mediated decay for mono-allelic expression of POLG

Frequency: Not found in 40 alleles from non-Alpers mitochondrial disease patients

Reference: (Chan et al., 2005b)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with A467T

Frequency: Not found in 40 alleles from non-Alpers mitochondrial disease patients

Reference: (Naviaux and Nguyen, 2004)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467 in and 18 mo. old male w/ mtDNA depletion

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Q879H 2637 g→t (exon 17) Liver failure and encephalopathy

Genetics: Found in cis with E1143G and in trans with A467T-T885S

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Alpers w/ valproate-induced hepatic failure

Genetics: Found in cis with E1143G and in trans with A467T-T885S in a 2 y.o. male

Frequency:

Reference: (McFarland et al., 2009)

Pubmed Link: PubMed

T885S 2653 a→t (exon 17) Alpers

Genetics: Found in cis with A467T and in trans with Q879H-E1143G

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Alpers w/ valproate-induced hepatic failure

Genetics: Found in cis with A467T, and in trans w/Q879H and E1143G

Frequency:

Reference: (McFarland et al., 2008)

Pubmed Link: PubMed

L886P 2657 t→c (exon 17) Alpers

Genetics: Found in trans w/ A467T

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

G888S 2662 g→a (exon 17) Alpers

Genetics: Compound heterozygous with L83P in 10 yr. old

Frequency:

Reference: (Bao et al., 2007) (Wong et al., 2008)

Pubmed Link: PubMed

G888D 2663 g→a (exon 17) Seizures and liver failure

Genetics: Found in trans w/ W748S in a 2 y.o. w/ seizures, hepatic failure, ketosis and abnormal MRI

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/L304R in a patient showing psychomotor retardation, epileptic encephalopathy, progressive cerebral atrophy, and altered liver enzymes.

Frequency: 1 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome

Reference: (Navarro-Sastre et al., 2012)

Pubmed Link: PubMed

A889T 2665 g→a (exon 17) PEO

Genetics: Sporadic / unknown Compound with R579W Compound with E1143G

Frequency: Filosto, 2003: not detected in 120 healthy control alleles

Reference: (Filosto et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Sporadic / unknown Compound with R579W Compound with E1143G

Frequency:

Reference: (Hisama et al., 2005)

Pubmed Link: PubMed

D892GfsX39 2675 ins g (exon 17)

Genetics: Found in trans w/ W748S in a 9 mo. old pt. with a deceased sibling.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

E895G 2684 a→g (exon 17) Myopathic MDS

Genetics: Found in one newborn with floppiness and 20% liver mtDNA depletion, heterozygous

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

T914A 2740 a→g (exon 18) Multiple Sclerosis-like illness

Genetics: 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.

Frequency:

Reference: (Echaniz-Laguana et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with A467T in a 9 mo. old with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

T914P 2740 a→c (exon 18) Alpers

Genetics: Found in trans with A467T.

Frequency: Not found in 300 control chromosomes

Reference: (Nguyen et al., 2006) 

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in trans with A467T in an 8 y.o. male w/encephalopathy and myoclonus .

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006) 

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with A467T in a 7 mo. female w/ Alpers

Frequency: Not found in 300 healthy French control chromosomes

Reference: (Naimi et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/ A467T

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

adPEO

Genetics: Heterozygous, Ptosis, exercise intolerance, fatigue, ragged red fibers

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: 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.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: In trans w/ A467T

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Epilepsy, myoclonic, and developmental delay

Genetics: ar, Found as a compound heterozygous mutation w/ A467T

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Epilepsy

Genetics: Found heterozygous with A467T in a 10 mo. old male with myoclonic seizures and jerks, and developmental regression.

Frequency:

Reference: (Dhamija et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with E1143G and W748S in a 2.5 y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in a 3 y.o. w/ seizures, hypotonia, encephalopathy, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ W748S in a 5 y.o. w/ seizures

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in a 5 y.o. w/ seizures, hearing loss, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ W748S in an 8 mo. w/ seizures, hypotonia, abnormal MRI, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in a 9 mo. w/ seizures, hypotonia, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures and liver failure

Genetics: Found in trans w/ A467T in a 4 y.o. with liver failure, seizures, and failure to thrive

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A467T in an 8 mo. w/ seizures, respiratory failure, and an abnormal MRI

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

MSCAE

Genetics: Found in trans w/ W748S in a 15 y.o. female with mitochondrial spinocerebellar ataxia and epilepsy.

Frequency:

Reference: (Hinnell et al., 2012)

Pubmed Link: PubMed

Alpers

Genetics: Found in compound with A467T in a 15 month female with mtDNA depletion

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in compound with W748S in a 6 yo male with epilepsy and hepatic cholestasis and cytolysis, and mtDNA deletions

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency:

Reference: (Roos et al., 2013)

Pubmed Link: PubMed

W918R 2752 t→c(exon 18) PEO with Parkinsonism

Genetics: ar, Compound (in trans) heterozygous with M430L

Frequency: Absent in 200 control alleles

Reference: (Invernizzi et al., 2008)

Pubmed Link: PubMed

PEO

Genetics: Found in trans with M430L in a 42 y.o. male with PEO and mtDNA

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

G923D 2768 g→a (exon 18) PEO

Genetics: Found as a homozygous mutation in 2 patients w/ mtDNA deletions. Also found as a heterozygous mutation with little or no symptoms.

Frequency: Lamantea, 2002: absent in 100 control DNA samples

Reference: (Lamantea et al., 2002)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency:

Reference: (Graziewicz et al., 2004)

Pubmed Link: PubMed

PEO

Genetics: Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci.

Frequency:

Reference: (Stuart et al., 2006)

Pubmed Link: PubMed

G923R 2767 c→g (exon 18)

Genetics: Reference # rs60636456

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=60636456

Pubmed Link: PubMed

K925R fs42X 2772_2773 delG Prematurity, epilepsy, deafness, retinitis pigmentosa, hemiparesis, and liver failure

Genetics: Found in trans w/A467T.

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

D930N 2788 g→a (exon 18) Alpers

Genetics: Infantile Alpers w/ bilateral lesions of thalami. Hepatocerebral MDS patient, Found in trans w/ W748S.

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

H932Y 2794 c→t (exon 18) PEO and mtDNA deletions

Genetics: Found in compound w/T251I/ P587L in1 pt. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions.

Frequency: Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians

Reference: (Di Fonzo et al., 2003)

Pubmed Link: PubMed

PEO

Genetics: Found in compound with G1051R in 2 family members PEO

Frequency: not seen in 120 control subjects.

Reference: (Mancuso et al., 2004a)

Pubmed Link: PubMed

Genetics: Isolated distal myopathy of the upper limbs w/ mtDNA depletion

Frequency:

Reference: (Giordano et al., 2010)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ P587L and T251I in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Peripheral Neuropathy

Genetics: Found in trans w/ T251I and P587L in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

S933R 2799 t→g (exon 18) PEO

Genetics: Found in trans w/ Q1214LX in a 60 y.o. w/ PEO, dementia, myopathy, and abnormal muscle histology

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ A957V in a 3 mo. w/ seizures, hypotonia, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R943C 2827 c→t (exon 18) Myocerebrohepatopathy

Genetics: In cis w/ E1143G and in trans w/G737R

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

PEO

Genetics: Ad, and premature ovarian failure

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

R943H 2828 g→a (exon 18) PEO

Genetics: ad PEO. Found in 2 siblings as a homozygous mutation

Frequency: Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians

Reference: (Lamantea et al., 2002)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency:

Reference: (Graziewicz et al., 2004)

Pubmed Link: PubMed

PEO

Genetics: Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci.

Frequency:

Reference: (Stuart et al., 2006)

Pubmed Link: PubMed

Premature ovarian failure

Genetics: Ad, and premature ovarian failure

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

PEO and Parkinsonism

Genetics: Found as a heterozygous mutation in a 63 y.o. male with PEO, resting tremors, dysarthria, and poly neuropathy, fatigue, hearing lass, and Parkinsonism

Frequency:

Reference: (Brandon et al., 2013)

Pubmed Link: PubMed

K947R 2840 g→a (exon 18) PEO and ovarian failure

Genetics: Compound heterozygote found w/ expansion of a polyQ (18Q) stretch.

Frequency:

Reference: (Baruffini et al., 2011)

Pubmed Link: PubMed

Y951N 2851 t→a (exon 18) Peripheral Neuropathy

Genetics: Found as a heterozygous mutation in 22 y.o. w/ peripheral neuropathy

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

3-methyl glutaconic aciduria

Genetics: Found as a heterozygous mutation in a 23 y.o. female with progressive muscle weakness, cataracts, and ovarian dysgenesis

Frequency:

Reference: (Bekheirnia et al., 2012)

Pubmed Link: PubMed

R953C 2857 c→t (exon 18) PEO

Genetics: ad

Frequency: Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes.

Reference: (Luoma et al., 2004)

Pubmed Link: PubMed

Genetics: Reference # rs11546842

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=11546842

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ W748S in a 51 y.o. w/ peripheral neuropathy, ptosis, hypotonia, ataxia, and seizures.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency:

Reference: (Gurgel-Giannetti et al., 2012)

Pubmed Link: PubMed

MNGIE-like

Genetics: Found in compound with W748S in a 50y.o. male with cognitive impairment, muscle weakness, diarrhea, vomiting, ptosis, and opthalmoparesis.

Frequency:

Reference: (Tang et al., 2012)

Pubmed Link: PubMed

Y955C 2864 a→g (exon 18) PEO

Genetics: ad PEO in a family w/ mtDNA deletions

Frequency: absent in 432 control chromosomes

Reference: (Van Goethem et al., 2001)

Pubmed Link: PubMed

PEO

Genetics: Found as a heterozygous mutation in 3 Belgian families w/ PEO

Frequency: Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians 

Reference: (Lamantea et al., 2002)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency:

Reference: (Graziewicz et al., 2004)

Pubmed Link: PubMed

Parkinsonism Premature ovarian failure Alzheimer's disease

Genetics: Most severe autosomal dominant mutation in POLG, drastically lowers polymerase catalysis, promotes stalling and errors in replication.

Frequency: Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes.

Reference: ( Luoma et al., 2004)

Pubmed Link: PubMed

PEO and Premature ovarian failure

Genetics: 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.

Frequency:

Reference: (Pagnamenta et al., 2006)

Pubmed Link: PubMed

PEO

Genetics: Studied recombinant protein and found that the Y955C POLG enzyme cause error-prone DNA synthesis

Frequency:

Reference: (Ponamarev et al., 2002)

Pubmed Link: PubMed

PEO

Genetics: Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci.

Frequency:

Reference: (Stuart et al., 2006)

Pubmed Link: PubMed

PEO

Genetics: Studied the yeast homologue that had mtDNA depletion and deletions with altered dNTP pools

Frequency:

Reference: (Baruffini et al., 2006)

Pubmed Link: PubMed

PEO

Genetics: Studied 4 pts. with adPEO and that were heterozygous for Y955C which revealed a low instance of mtDNA point mutations.

Frequency:

Reference: (Kollberg et al., 2005)

Pubmed Link: PubMed

PEO

Genetics: Y955C POLG was targeted transgenically to the murine heart. The mice had cardiomyopathy and mtDNA depletion.

Frequency:

Reference: (Lewis et al., 2007)

Pubmed Link: PubMed

PEO/Alzheimer's

Genetics: Myopathy, COX deficient muscle fibers, and mtDNA depletion found in 2 siblings who developed Alzheimer's and thought to have aged prematurely.

Frequency:

Reference: (Melberg et al., 2005)

Pubmed Link: PubMed

Genetics: Found as a heterozygous mutation w/ hearing loss, failure to thrive, generalized ETC complex deficiency

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

PEO

Genetics: Found in cis w/ G517V in a 47 y.o. w/ PEO, ptosis, myopathy, and neuropathy

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found as a heterozygous mutation in a 45 y.o. w/ myopathy and PEO

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in a Chinese population with Parkinsonism at an allelic frequency of 0.816

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

PEO and Parkinsonism

Genetics: Found as heterozygous mutations in siblings in Japan

Frequency:

Reference: (Mukai et al., 2013)

Pubmed Link: PubMed

A957S 2869 g→t (exon 18) PEO

Genetics: Found as both a heterozygous and as a homozygous mutation in one individual in two Sicilian families.

Frequency: Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians

Reference: (Lamantea et al., 2002)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency:

Reference: (Graziewicz et al., 2004)

Pubmed Link: PubMed

PEO

Genetics: Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci.

Frequency:

Reference: (Stuart et al., 2006)

Pubmed Link: PubMed

A957P 2869 g→c (exon 18) Alpers

Genetics: Found in compound w/A467T in a 8 mo. old male w/ multiple complex deficiencies

Frequency: 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

Reference: (de Vries et al., 2007)

Pubmed Link: PubMed

Alpers

Genetics: Found in compound w/A467T in a 6 mo. old w/ infantile hepatocereberal syndrome.

Frequency: Ferrari, 2005: absent in 200 consecutive control individuals from Northern continental Europe as well as 350 Italian controls

Reference: (Ferrari et al., 2005)

Pubmed Link: PubMed

Epilepsy, liver failure, occipital strokes, and growth retardation

Genetics: ar, found as a compound heterozygous mutation w/ A467T

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

A957V 2870 c→t (exon 18) Seizures

Genetics: Found in trans w/ C1077G in a 2 y.o. w/ seizures, encephalopathy, and hypotonia

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Genetics: Found in trans w/ G737R in a 4 mo. Symptoms not noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ S933R in a 3 mo. w/ seizures, hypotonia, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

F961S 2882 t → c (exon 18) PEO

Genetics: ad PEO

Frequency:

Reference: (Adachi et al., 2002)

Pubmed Link: PubMed

A962T 2884 g→a (exon 18) Ataxia

Genetics: Found in trans w/ R964C in a 14 y.o. w/ ataxia, muscle weakness, and central hypoventilation

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R964C 2890 c → t (exon 18) Mitochondrial toxicity susceptibility to NRTIs

Genetics: Found in a HIV1 patient with hyperlactatemia following 1 yr. of d4T and 3TC anti-viral treatment

Frequency: Not found in 26 Thai HIV-1-infected individuals, or 110 healthy volunteers

Reference: (Yamanaka et al., 2007)

Pubmed Link: PubMed

Ataxia Neuropathy

Genetics: Found in trans w/ A862T, and found as a heterozygous mutation w/ ataxia and hypotonia

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Cerebellar ataxia, neuropathy, epilepsy, and restless leg syndrome

Genetics: Found heterozygous with A862T in 2 siblings that died in their early 20’s

Frequency:

Reference: (Stricker et al., 2009)

Pubmed Link: PubMed

Ataxia

Genetics: Found in trans w/ A962T in a 14 y.o. w/ ataxia, muscle weakness, and central hypoventilation

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

L965X 2894 t→g (exon 18) PEO

Genetics: ar, found in cis with E1143G and in trans with R627Q-Q1236H

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

L966R 2897 t→g (exon 18) Alpers

Genetics: Compound with A467T

Frequency: Not found in 300 control chromosomes

Reference: (Nguyen et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: In trans w/A467T.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 1 y.o. w/ seizures and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 1 y.o. w/ seizures and developmentally delayed

Frequency:

Reference: (Hunter et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/A467T in a 17 mo. old male with seizures and encephalopathy

Frequency:

Reference: (McCoy et al., 2011)

Pubmed Link: PubMed

G975stop 2923 c→t (exon 18) Seizures

Genetics: Found as a heterozygous mutation in a 6 yo female with dystonia, psychomotor delay, and seizures

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

S998W 2993 c→g (exon 19)

Genetics: Reference # rs79840247

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=79840247

Pubmed Link: PubMed

S998L 2993 c→t (exon 19) PEO

Genetics: Found as a compound heterozygote with D1184H in a 64 y.o. female with PEO, bilateral ptosis, and encephalopathy.

Frequency:

Reference: (Martikainen et al.,)

Pubmed Link: PubMed

W1020X 3057 g→a (exon 19) Alpers

Genetics: Compound with A467T

Frequency:

Reference: (Nguyen et al., 2005)

Pubmed Link: PubMed

Q1024X 3067 c→t (exon 20) Seizures

Genetics: Found in trans w/ A467T in a 2 y.o. w/seizures, hearing loss, and hemiparesis

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

c. 3104 +3a→t 3104 +3a→t (splice variant between ex. 19 and 20) PEO

Genetics: Found in trans w/ F749S in a 66 y.o. w/ PEO, ptosis, myopathy, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Optic atrophy

Genetics: 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.

Frequency:

Reference: (Milone et al., 2011)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ G848S in a 63 y.o. w/ PEO, ptosis, hearing loss, muscle weakness and ragged red fibers

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

3104 +3a→t (splice variant resulting in a deletion on exon 19) PEO

Genetics: 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.

Frequency:

Reference: (Roos et al., 2013)

Pubmed Link: PubMed

V1044A 3131 t→c (exon 20) Alpers

Genetics: Found in trans with R722H in a 2.5 y.o. old with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

R1047Q 3140 g→a (exon 20) PEO

Genetics: Sporadic / unknown

Frequency: Not found in 250 control individuals

Reference: (Agostino et al., 2003)

Pubmed Link: PubMed

R1047W 3139 c→t (exon 20) Alpers

Genetics: Compound in trans with T851A

Frequency: Not found in over 200 control alleles

Reference: (Wiltshire et al., 2008)

Pubmed Link: PubMed

PEO

Genetics: ar, in trans w/ A862T

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ A862T in a 61 y.o. female with PEO, ptosis, peripheral neuropathy, ataxia, and dysarthria.

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

K1050RfsX44 3149 del a (exon 20) Seizures

Genetics: Found in trans w/ A467T in a 4 y.o. w/ seizures, ataxia, hypotonia, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

G1051R 3151 g→c (exon 20) PEO, SANDO

Genetics: ar Found as compound with H932Y

Frequency: not seen in 120 control subjects.

Reference: (Mancuso et al., 2004a)

Pubmed Link: PubMed

P1073L 3218 c→t (exon 20) Hepatocerebral - Alpers symptoms

Genetics: 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.

Frequency:

Reference: (Kurt et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found as a compound heterozygote w/ S305R in a 9 mo. pt. w/ Alpers

Frequency:

Reference: (Baruffini et al., 2011)

Pubmed Link: PubMed

Failure to thrive

Genetics: Found in trans w/ G848S in a 2 y.o. w/ hypotonia, and gastro-esophageal reflux.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Myopathy

Genetics: Found as a heterozygous mutation in a 5 yo female with epilepsy, myopathy, and tubulopathy

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

G1076V 3227 g→t (exon 20) PEO

Genetics: Sporadic / unknown

Frequency: Not detected in 120 healthy control alleles

Reference: (Filosto et al., 2003)

Pubmed Link: PubMed

C1077G 3229 t →g (exon 20) Seizures

Genetics: Found in trans w/ A957V in a 2 y.o. w/ seizures, encephalopathy, and hypotonia

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

I1079L 3235 a→c (exon 20) adPEO

Genetics: Heterozygous Hearing loss, and ptosis

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

S1080T 3239 g→c (exon 20) Intracranial calcifications

Genetics: A 55 y.o. female with action tremors, peripheral neuropathy, hearing loss, and intracranial calcifications

Frequency:

Reference: (Sidirooulos et al., 2013)

Pubmed Link: PubMed

S1080I 3239 g→t (exon 20) Epilepsy

Genetics: Found in compound with L79F in an 8 yo female with adrenocortical insufficiency and hypothyroidy

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

Epilepsy

Genetics: Found in compound with L79F in an 8 yo female with epilepsy, cerebellar ataxia, and ptosis

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

R1081dup 3240– 3242 ins ccg (R) (exon 20) Alpers

Genetics: Found in cis w/ L392V and in trans w/L304R

Frequency:

Reference: (Cardenas et al., 2010)

Pubmed Link: PubMed

Seizures

Genetics: Found in trans w/ L304R in a 1 y.o. w/ seizures and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R1081Q 3241 c→g (exon 20) Alpers-like

Genetics: Found in trans with A862T in a 7 y.o. male with Alpers-like symptoms.

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

Alpers-like

Genetics: Found in trans with A862T in a 4 y.o. male with Alpers-like symptoms. Affected sibling

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

Cerebellar ataxia

Genetics: Found as a heterozygote in a 29 y.o. female with cerebellar ataxia and diabetes

Frequency:

Reference: (Ferreira et al., 2011)

Pubmed Link: PubMed

R1081P 3242 g→c (exon 21) PEO

Genetics: Found in trans w/ L304R in a 10 y.o. w/ ataxia, seizures, PEO, and dystonia

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

F1092L 3276 t→g (exon 21)

Genetics: Reference # rs74034411

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=74034411

Pubmed Link: PubMed

S1095R 3285 c→g (exon 21) adPEO

Genetics: Hearing loss, ptosis, Muscle weakness, optic atrophy

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

3286 c→g (exon 21) Failure to thrive

Genetics: ar, found in trans w/ D1184N. Aslo, impaired liver functions, deafness, and demyelating sensomotor neuropathy

Frequency: <0.5% of Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Hepatic failure

Genetics: Found in trans w/ A467T in a 6 mo. w/ hypotonia, liver failure, abnormal muscle histology, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R1096C 3286 c→t (exon 21) PEO

Genetics: Sporadic or ar in PEO

Frequency: Agostino 2003: Not found in 250 individuals

Reference: (Agostino et al., 2003)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans with P648R in PEO-myopathy. Found as homozygous mutation with Q1236H in Alpers

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found as compound w/ Q1236H .

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/T914P, and homozygous in a 2nd pt.

Frequency:

Reference: (Ashley et al., 2008) and a correction in (Ashley et al., 2009)

Pubmed Link: PubMed

Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia

Genetics: Found with R627Q in a 43 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

Seizures

Genetics: Found as a homozygote in an 8 mo. old pt. with encephalopathy and seizures.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found as a homozygote in a 1 y.o. with seizures and liver failure.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in trans w/ G848S in a 2 y.o. w/ hypotonia, ptosis, hepatic failure, and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

Seizures

Genetics: Found as a homozygote in a 2 y.o. w/ seizures, lactic acidosis and developmentally delayed.

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

SANDO

Genetics: Found in trans w/L591F in a 48 y.o. female with SANDO and dysphagia.

Frequency:

Reference: (Kurt et al. 2012)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ W748S in a 49 y.o. male with PEO, ptosis, epilepsy and peripheral neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/A467T in a 42 y.o. male with PEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

R1096H 3287 g→a (exon 21) Alpers

Genetics: Found as a compound in trans with R627Q

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

S1104C 3311 c→g (exon 21) PEO

Genetics: Sporadic / unknown Found as compound with A467T

Frequency: Not found in 250 individuals

Reference: (Agostino et al., 2003)

Pubmed Link: PubMed

Parkinsonism

Genetics: Found in trans w/G848S in a 59 y.o. male with mtDNA deletions and cerebellar ataxia

Frequency:

Reference: (Lax et al., 2012b)

Pubmed Link: PubMed

S1104F 3311 c→t (exon 21) Epilepsy

Genetics: 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.

Frequency:

Reference: (Sitarz et al., 2014)

Pubmed Link: PubMed

A1105T 3313 g→a (exon 21) PEO

Genetics: Found as a heterozygous mutation and as a compound heterozygous mutation w/ N468D in 3 patients of the same family all w/PEO

Frequency: Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes.

Reference: (Luoma et al., 2004)

Pubmed Link: PubMed

PEO

Genetics: 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.

Frequency:

Reference: (Wanrooij et al., 2004)

Pubmed Link: PubMed

V1106I 3316 g→a (exon 21) PEO

Genetics: ar, found in trans with T251I-P587L

Frequency: Not found in 500 Italian controls.

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

H1110Y 3328 c→t (exon 21) infantile hepatocerebral mtDNA depletion

Genetics: Heterozygous, found in cis Q1236H, & in trans w/ W748S+ E1143G

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

L1113P 3338 t→c (exon 21) Seizures

Genetics: Found in trans w/ A467T in a 1 y.o. with encephalopathy, seizures, and hepatic failure

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R1128H 3383g→a (exon 21) Microcephaly

Genetics: Heterozygous, found w/ G517V

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

H1134R 3401 a→g (exon 21) infantile hepatocerebral mtDNA depletion

Genetics: Heterozygous, found in trans with Y831C

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

E1136K 3406 g→a (exon 21) infantile hepatocerebral mtDNA depletion

Genetics: Heterozygous, found T251I+P587L

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Genetics: Reference # 56047213

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=56047213

Pubmed Link: PubMed

R1138C 3412 c→t (exon 21) PEO

Genetics: Found in trans w/ A467T

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

R1142W 3424 c→t (exon 21) Neutral polymorphism

Genetics:

Frequency: 0.6% of 450 individuals

Reference: (GeneSNPs, 2004)

Pubmed Link: PubMed

Genetics: Reference # rs2307442

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307442

Pubmed Link: PubMed

E1143G 3428 a→g (exon 21) Neutral polymorphism

Genetics: Neutral polymorphism but may modulate disease mutations

Frequency: SNP at 3.7% of 450 individuals of European descent. Not found in Asian or African populations 

Reference: (GeneSNPs, 2004) 

Pubmed Link: PubMed

PEO

Genetics: Found as a heterozygous mutation

Frequency: Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians

Reference: (Di Fonzo et al., 2003)

Pubmed Link: PubMed

Ataxia

Genetics: Found as a homozygous and heterozygous mutation, or in compound w/ W748S all within the same family

Frequency:

Reference: (Van Goethem et al., 2004)

Pubmed Link: PubMed

Neutral polymorphism but may modulate disease mutations

Genetics: Found in cis w/ A889T

Frequency:

Reference: (Hisama et al., 2005) 

Pubmed Link: PubMed

Ataxia

Genetics: Found as a homozygous mutation w/ W748S

Frequency: Carrier frequency in the general Finnish population of 1:125 from 500 control chromosomes

Reference: (Hakonen et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: Found in trans w/G848S and in cis w/E1143G in 4 children w/ hepatocerebral disorders and mtDNA depletion

Frequency: Present in 3-5% of the control population

Reference: (Davidzon et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: Found in ataxia-neuropathy in cis with W748S and in compound with G848S or A467T. 

Frequency:

Reference: (Nguyen et al., 2005)

Pubmed Link: PubMed

Ataxia

Genetics: Found in compound w/ Q497H and W748S

Frequency: frequency of 0.03

Reference: (Winterthun et al., 2005) 

Pubmed Link: PubMed

Ataxia-neuropathy spectrum disorders

Genetics: Studied the biochemical effects of E1143G in cis with other pathogenic mutations, and how it can modulate the effects of these mutations

Frequency:

Reference: (Chan et al., 2006)

Pubmed Link: PubMed

Liver failure, Neuropathy, and PEO

Genetics: 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.

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

Encephalopathy

Genetics: Found in compound w/ W748S, A467T R323H, and M1163R in children w/ progressive encephalopathy

Frequency: Not found in 200 control alleles

Reference: (Kollberg et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found in compound w/ W748S and nt2842_2843insA in children w/ multiple complex deficiencies

Frequency: 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.

Reference: (Sarzi, et al. 2007)

Pubmed Link: PubMed

Alpers with valproate-induced hepatic failure

Genetics: Found in cis w/ T885S and A467T, and in trans w/ Q879H

Frequency:

Reference: (McFarland et al., 2008)

Pubmed Link: PubMed

Alpers, Ataxia Neuropathy, and arPEO+ Myocerbrohepatopathy (MCHS)

Genetics: 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.

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

PEO and Ataxia

Genetics: 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.

Frequency:

Reference: (Stewart et al., 2009)

Pubmed Link: PubMed

mtDNA depletion

Genetics: In cis w/ W748S and in trans w/ H1110Y+Q1236H

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: In cis w/W748S and in trans w/G848S

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis w/ Q497H and W748S, and in trans w/ G848S.

Frequency: Found in one child with a normal brain MRI.

Reference: (Brunetti-Pierri et al., 2008)

Pubmed Link: PubMed

Lipodystrophy

Genetics: Increase susceptibility of HIV pt. treated w/D4T to develop lipodystrophy

Frequency:

Reference: (Chiappini, et al., 2009)

Pubmed Link: PubMed

PEO, ptosis, polyneuropathy, ataxia, and dysarthria

Genetics: Found in compound w/ A467T and W748S

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Epilepsy and myoclonic

Genetics: ar, found w/ A467T

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

Genetics: Reference # rs2307441

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307441

Pubmed Link: PubMed

SANDO

Genetics: Found in trans with A467T and in cis with W748S. Sensory ataxia, dysarthria, and opthalmoplegia.

Frequency:

Reference: (Posada et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with W748S and in trans with R807C in a 1y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with Q497H and W748S, and in trans with A467T in a 6 y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with W748S and in trans with G8484S in a 11 mo. old with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

Alpers

Genetics: Found in cis with W748S and in trans with T914P in a 2.5 y.o. with epilepsy and encephalopathy

Frequency: 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples

Reference: (Isohanni et al., 2011)

Pubmed Link: PubMed

VPA-induced liver toxicity

Genetics: Found in 2 patients ages 26 and 33 with VPA-induced hepatotoxicity as a heterozygous mutation

Frequency: A frequency 1.9x10e-4 out of 968 alleles of ethnically matched population controls

Reference: (Stewart et al., 2010)

Pubmed Link: PubMed

Alpers

Genetics: Found w/R232H and W748S in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

Alpers

Genetics: Found w/M1163R and W748S in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

MIRAS

Genetics: 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.

Frequency: Frequencies in Europe for W748S+E1143G or A467T range from 0.6% in Belgium, 0.8% in Finland, and 2% in Finland

Reference: (Palin et al., 2012)

Pubmed Link: PubMed

D1145GfsX9 gagg ins at 3433 /3434 (exon 21) Seizures

Genetics: Found in trans w/ L304R in a 12 y.o. with hypotonia and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

R1146C 3436 c→t (exon 21) Neutral polymorphism

Genetics: SNP

Frequency: 0.6% of 450 individuals

Reference: (GeneSNPs, 2004)

Pubmed Link: PubMed

Neutral polymorphism

Genetics: Found as a heterozygous mutation in a 18 y.o. male with muscle atrophy

Frequency: 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population.

Reference: (Gonzalez-Vioque et al., 2006)

Pubmed Link: PubMed

Genetics: Reference # rs2307440

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307440

Pubmed Link: PubMed

N1157S 3470 a→g (exon 21) ?

Genetics: Found in trans w/ T251I and P587L in a 9 y.o. w/ no symptoms noted

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

c.3482 +2t>c 3482 +2t's splice at intron 21 (exon 21) Alpers

Genetics: Exon21/Intron21 splice site mutation at a.a. 1161. Found in trans with A467T in a male child w/ infantile hepatocerbral syndrome

Frequency:

Reference: (Ferrari et al., 2005)

Pubmed Link: PubMed

M1163R 3488 t→g (exon 22) Liver failure, encephalopathy, and epilepsy

Genetics: Found as compound in trans with W748S - E1143G

Frequency: Not found in 200 control alleles

Reference: (Kollberg et al., 2006)

Pubmed Link: PubMed

Alpers

Genetics: Found w/E1143G and W748S in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement

Frequency:

Reference: (Sofou et al., 2012)

Pubmed Link: PubMed

F1164I 3490 t→a (exon 22) PEO

Genetics: Ar, found in cis with T914P and in trans with Q308H

Frequency: Not found in 200 Italian controls

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

F1164L 3492 t→ g or a (exon 22)

Genetics: Reference # rs62640038

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640038

Pubmed Link: PubMed

L1173fsX 3518 ins gact, fs in exon 22 (exon 22) Alpers

Genetics: Compound with A467T

Frequency: Not found in 300 control chromosomes

Reference: (Nguyen et al., 2006)

Pubmed Link: PubMed

Q1175R 3524 a→g (exon 22) SNP

Genetics: Reference # rs188348569

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusID=5428

Pubmed Link: PubMed

S1176L 3527 c→t (exon 22) PEO

Genetics: Found as a heterozygous mutation

Frequency: Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians

Reference: (Lamantea et al., 2002)

Pubmed Link: PubMed

PEO

Genetics: Found in compound w/with T251I/P587L

Frequency:

Reference: (Lamantea and Zeviani, 2004)

Pubmed Link: PubMed

D1184L 3550 g→c (exon 22) PEO

Genetics: Found as a compound heterozygote with S998L in a 64 y.o. female with PEO, bilateral ptosis, and encephalopathy.

Frequency:

Reference: (Martikainen et al., 2010)

Pubmed Link: PubMed

C1188R 3562 t→c (exon 22) Seizures

Genetics: Found in trans w/ A467T in a 3 y.o. w/ seizures, hypotonia, and developmentally delayed

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

D1184N 3550 g→a (exon 22) PEO and tetraparesis

Genetics: Compound in trans with N468D

Frequency: 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population.

Reference: (Gonzalez - Vioque et al., 2006)

Pubmed Link: PubMed

Multi-system disorder

Genetics: Found in compound with R227W in 2 children w/ severe childhood multi-system disorder

Frequency: 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

Reference: (de Vries et al., 2007)

Pubmed Link: PubMed

Failure to thrive

Genetics: ar, found in trans w/ S1095R. Aslo, impaired liver functions, deafness, and demyelating sensomotor neuropathy

Frequency: <0.5% in Dutch population

Reference: (Blok and van den Bosch et al., 2009)

Pubmed Link: PubMed

PEO

Genetics: Found as a heterozygous mutation in a 70 yo male with PEO, neuronopathy, and parkinsonism

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

PEO

Genetics: Found as a heterozygous mutation in a 75 yo male with PEO and neuronopathy

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

R1187W 3559 c→t (exon 22)

Genetics: Found in a patient with mitochondrial depletion syndrome and T cell immunodeficiency. Pathogenesis unclear.

Frequency: Not detected in 100 Turkish control alleles

Reference: (Reichenbach et al., 2006)

Pubmed Link: PubMed

Hepatic failure

Genetics: Found as a heterozygous mutation in a 10 yo male with hepatic failure, myopathy and psychomotor delay

Frequency: Found in 160 French cohort of potential POLG patients

Reference: (Rouzier et al., 2013)

Pubmed Link: PubMed

K1191N 3573 g→t (exon 22) Alpers

Genetics: Compound in trans with A467T

Frequency: Not found in 250 control individuals

Reference: (Horvath et al., 2006)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/ T251I and P587L in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

K1191R 3572 a→g (exon 22) Myocerebrohepatopathy

Genetics: In trans with T251I-P587L

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

D1196N 3586 g→a (exon 22) Myopathy

Genetics: In trans w/ G517V

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

T1199X 3595 ins. a (exon 22) Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia

Genetics: Found with R627Q in a 47 yr. old patient

Frequency:

Reference: (Schulte et al., 2009)

Pubmed Link: PubMed

c.3600 del T 3600 deletion of t (exon 22) Epilepsy

Genetics: 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.

Frequency:

Reference: (Sitarz et al., 2014)

Pubmed Link: PubMed

G1205A 3614 g→ c (exon 22)

Genetics: Heterozygous w/ Retinitis pigmentosa, hearing loss, failure to thrive

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

Y1210fs6X 3630 ins c (exon 22) Infantile Hepatocerebral Syndrome

Genetics: Compound in trans with W748S - E1143G, Mutation causes frame shift to stop at a.a. 1225

Frequency:

Reference: (Ferrari et al., 2005)

Pubmed Link: PubMed

Alpers

Genetics: Found in 2 infants in trans w/ W748S

Frequency:

Reference: (Spinazzola et al., 2009)

Pubmed Link: PubMed

Q1214X 3640 c→t (exon 22) PEO

Genetics: Found in trans w/ S933R in a 60 y.o. w/ PEO, dementia, myopathy, and abnormal muscle histology

Frequency: Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies.

Reference: (Tang et al., 2011)

Pubmed Link: PubMed

c.3643+2t>c 3645 t→c splice variant(exon 22/23) Alpers

Genetics: Found in trans w/ A467T

Frequency:

Reference: (Roels, et al., 2009)

Pubmed Link: PubMed

S1230F 3689 c→t (exon 23) Neutral polymorphism

Genetics:

Frequency: <1 % in control populations

Reference: (Luoma et al., 2007)

Pubmed Link: PubMed

Genetics: Found in a Chinese population with Parkinsonism at an allelic frequency of 0.453

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

Q1236H 3708 g→t (exon 23) Neutral polymorphism

Genetics:

Frequency: 4.0% of 450 individuals

Reference: (GeneSNPs, 2004) 

Pubmed Link: PubMed

Neutral polymorphism

Genetics: Found in 5 PEO patients as a heterozygous mutation

Frequency: Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians

Reference: (Di Fonzo et al., 2003) 

Pubmed Link: PubMed

Neutral polymorphism

Genetics: Found in cis with R627Q in trans with A467T in a family w/ ataxia - myopathy and ptosis

Frequency:

Reference: (Luoma et al., 2005)

Pubmed Link: PubMed

3711 g→t (exon 23) Alpers

Genetics: Found in trans with A467T, and in cis w/ T849H. Also found as a compound w/ R1096C.

Frequency:

Reference: (Wong et al., 2008)

Pubmed Link: PubMed

mtDNA depletion

Genetics: In cis w/ H1110Y and in trans w/ E1143G+W748S

Frequency:

Reference: (Taanman et al., 2008)

Pubmed Link: PubMed

Genetics: Reference # rs3087374

Frequency:

Reference: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=3087374

Pubmed Link: PubMed

VPA induced liver toxicity

Genetics: Found in 5 patients ages 2 to 47 with VPA-induced hepatotoxicity as a heterozygous mutation

Frequency: A frequency 1.9x10e-4 out of 968 alleles of ethnically matched population controls

Reference: (Stewart et al., 2010)

Pubmed Link: PubMed

Genetics: Found in a Chinese population with Parkinsonism at an allelic frequency of 0.281

Frequency: 344 Chinese parkinson patients and 144 controls

Reference: (Gui et al., 2012)

Pubmed Link: PubMed

X1240Q+35a.a. 3718 t→c +35aa (exon 23) PEO

Genetics: Found in trans w/A467T in a 59 y.o. male with arPEO and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012b)

Pubmed Link: PubMed

PEO

Genetics: Found in trans w/A467T in a 59 y.o. male with arPEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

X1240Y+35a.a. 3720 g→c +35aa (exon 23) PEO

Genetics: Found in trans w/A467T in a 42 y.o. female with PEO, ptosis and sensory neuropathy

Frequency:

Reference: (Lax et al., 2012a)

Pubmed Link: PubMed

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