Human DNA Polymerase Gamma Mutation Database
Human DNA polymerase is composed of two subunits, a 140 kDa catalytic subunit encoded by the POLG on chromosome 15q25, and a 55kDa accessory subunit encoded by the POLG2 gene on chromosome 17q23-24.
A number of mutations have been mapped to the gene for the catalytic subunit of DNA polymerase, POLG, and found to be associated with mitochondrial diseases.
This database lists all known mutations in the coding region of the POLG gene and describes the associated disease. This list is maintained by the Mitochondrial DNA Replication Group at NIEHS.
The nucleotide changes are numbered from the initiation Methionine codon and are based on the cDNA (accession U60325.1) and gene sequence (accession AF497906.1).
All inquiries, additions to the list, and comments should be made to Bill Copeland or Maggie Humble.
Alignment Document (132 KB)
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Visual overview of the POLG mutations. Download larger view. (670 KB)
| Amino Acid Substitution | cDNA position | Disease | Details | Frequency | Reference | Link to PubMed |
|---|---|---|---|---|---|---|
| R3P | 8 g→c (exon 2) | PEO | ar | (Van Goethem et al., 2001) reported 0 out of 229 control Individuals (<0.4%) | (Van Goethem et al., 2001) | PubMed |
| G11D | 32 g→a (exon 2) | Ataxia Neuropathy | Found in cis with R627Q and in trans with R852C, and also found as a Heterozygous mutation with a failure to thrive | (Wong et al., 2008) | PubMed | |
| Alpers | Found in cis w/ R852C and in trans w/ W748S. In a second pt. found in cis w/R852C and in trans w/ A467T. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Alpers | Found in cis w/ R852C and in trans w/ A467T. In a 2nd pt., found in cis w/ R852C and in trans w/ W748S and E1143G | (Stewart et al., 2009) | PubMed | |||
| Leigh Syndrome | Found in cis with R852C and in trans with W748S | (Naess et al., 2009) | PubMed | |||
| Multiple system atrophy | Found with R852C in a 58 y.o. female with progressive cerebellar atrophy. Pt. had mtDNA deletions and mtDNA depletion. | (Mehta et al., 2011) | PubMed | |||
| Seizures and liver failure | Found in trans w/ A467T and in cis w/ R852C in an 8 mo. w/ seizures, liver failure, and lactic acidosis. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Encephalopathy | Found in cis w/ R852C and in trans w/ R627Q in a 25 y.o. w/ dementia, encephalopathy, and stroke. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| P18S | 52 t→g (exon 2) | Neutral polymorphism | 0.6% of 450 individuals | (GeneSNPs, 2004) | PubMed | |
| S28C | 82 a→t (exon 2) | PEO | Found in a 25 y.o. pt. that is homozygous for the W748S mutation with PEO, ataxia, ptosis, and hearing loss | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| R42X | 125 del (exon 2) | Reference # rs59510277 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=59510277 | PubMed | ||
| ±Glu at aa 43-52 | ±(CAG)n at nucleotides 126 to 157 (exon 2) | Male infertility, testicular cancer | Identified an association between absence of the common, ten CAG repeat allele and male infertility due to a range of sperm quality defects. | Rovio et al., 2001 reported 88% of both Finnish and ethnically mixed populations carry the predominant allele of 10 CAG repeats | (Rovio et al., 2001) | PubMed |
| Male infertility, testicular cancer | Predictive value for infertility in a man homozygous for the POLG CAG polymorphism was 15.5% (95% CI: 4.8-51%). There was a positive association with sperm concentration. | studied in 1298 male subjects: 429 patients with infertility/subfertility, and 869 controls (495 men from the general population with unknown fertility and 374 recent fathers) | (Jensen et al., 2004) | PubMed | ||
| Male infertility, testicular cancer | The human DNA POL gamma is unique in that the first exon of the gene contains a CAG10 trinucleotide repeat. | (Ropp and Copeland, 1996) | PubMed | |||
| Male infertility, testicular cancer | Micro-deletion in the Y chromosome frequency in France, averaged: 10–15% in cases of azoospermia, and 5–10% in cases of oligozoospermia. | (Aknin-Seifer et al., 2005) | PubMed | |||
| Male infertility, testicular cancer | Suggested that the POLG1 CAG-repeat polymorphisms does not contribute to oligozoospermia in French and Italian populations. | 625 individuals in three groups of case-controls from three different Italian regions | (Brusco et al., 2006) | PubMed | ||
| Male infertility, testicular cancer | 80 normozoospermic and 124 non-normozoospermic semen samples were analyzed for nucleotide substitutions. There were no significant differences in the frequencies of nucleotide substitution and POLgamma genotypes in the two groups. | (Harris et al., 2006) | PubMed | |||
| Male infertility, testicular cancer | The mutated genotype was found at the same frequency in both infertile and normospermic Italian men. | (Krausz et al., 2004) | PubMed | |||
| Male infertility, testicular cancer | The heterozygosity level ranges from 22% in Europe to 13.6% in Southwest Asia with the lowest value of 7.4% in Siberia/East Asia. Found an extremely low variability of the trinucleotide CAG microsatellite repeats. | The population sample consisted of 1,330 individuals from 3 large geographic areas: Europe, Southwest Asia, and Siberia/East Asia. | (Malyarchuk et al., 2005) | PubMed | ||
| Male infertility, testicular cancer | Studied CAG repeat length variation at the POLG gene locus in a group of patients with testicular tumors compared with an equivalent healthy Polish male population. The CAG repeats in the POLG gene were significantly more frequent in testicular cancer patients than in healthy men (26% versus 11%, P=0.035 by the Fisher exact test). | Nowak et al., 2005 reported 11% healthy Polish men (n=55) were heterozygous, and 26% of testicular cancer patients (n=49) were heterozygous for the CAG repeats ≠ 10. With no clinical differences in tumor pathology. | (Nowak et al., 2005) | PubMed | ||
| Idiopathic sporadic Parkinson | Increase frequency of non-10/11 (CAG) variant in Parkinson disease (PD) | Luoma, 2007: found in 10% PD patients compared with 3.5-4.3% spouse/population controls. | (Luoma et al., 2007) | PubMed | ||
| Seminoma testicular cancer | Homozygous lack of 10 CAG repeat | 4.9% of Danish men (n=869). 96.7% of Seminoma pts. | (Jensen et al., 2008) | PubMed | ||
| Friedreich's Ataxia | Age of onset of FRDA is inversely correlated to the POLG CAG repeats | Study done in 49 Iranian FRDA pts. | (Heidari et al., 2008) | PubMed | ||
| Sporadic Parkinson | CAG repeat region screened in 243 Swedish Parkinson’s pts. An assoc. was found with repeats in glutamine runs that were not 10 or 11 in number. | 243 Swedish PD patients and 279 Swedish controls | (Anvret, et al., 2010) | PubMed | ||
| PEO and ovarian failure | Compound heterozygote found w/ K947R | (Baruffini et al., 2011) | PubMed | |||
| Q43R | 128 a→g (exon 2) | Idiopathic sporadic Parkinson | (Luoma et al., 2007) | PubMed | ||
| Reference # rs28567406 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=28567406 | PubMed | ||||
| Q44X | 132 del gc (exon 2) | Reference # rs35424491 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=35424491 | PubMed | ||
| Q45R | 134 a→g (exon 2) | Epilepsy | Found in trans w/ D136E | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed |
| Q49E | 145 c→g (exon 2) | Neutral polymorphism | <1 % in control populations | (Luoma et al., 2007) | PubMed | |
| Q49X | 147 del gc (exon 2) | Reference # rs72434227 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=72434227 | PubMed | ||
| Q50X | 149 del ag (exon 2) | Reference # rs71879812 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=71879812 | PubMed | ||
| Q53X | 158 del aa (exon 2) | Reference # rs41550117 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=41550117 | PubMed | ||
| S64L | 191 c→t (exon 2) | Found in cis with R232H in ar Charcot-Marie-Tooth | 30.6% of control population (90/294 control alleles) | (Harrower et al, 2008) | PubMed | |
| Q68X | 202 c→t (exon 2) | Alpers | Found in trans w/ A467T | (Wong et al., 2008) | PubMed | |
| L83P | 248 t→c (exon 2) | Alpers | Compound heterozygous mutation with G888S in 10 yr. old | (Bao et al., 2008) | PubMed | |
| (Wong et al., 2008) | PubMed | |||||
| F88L | 264 c→g (exon 2) | Found in trans w/ A467T in a 42 y.o. w/ no symptoms noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |
| H110Y | 328 c→t (exon 2) | Heterozygous, hypotonia, failure to thrive, short stature, respiratory failure | (Wong et al., 2008) | PubMed | ||
| W113G | 337 t→g (exon 2) | Reference # rs77321104 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=77321104 | PubMed | ||
| D136E | 408 c→g (exon 2) | Epilepsy | Found in trans w/ Q45R | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed |
| A143V | 427 g→t (exon 2) | Alpers | Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA | (Sarzi et al. 2007) | PubMed | |
| PEO | Found in trans w/ L304R in a 22 y.o. pt. with PEO and cerebral cavernous malformation. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ G848S in a 4 y.o. w/ hypotonia, encephalopathy, seizures, hepatic failure, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ G848S in a 38 y.o. w/ ataxia, peripheral neuropathy, hearing loss, and seizures | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in an 8 y.o. w/ seizures and an abnormal MRI | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ G848S in a 37 y.o. symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| PEO | Found in trans w/ A467T in a 49 y.o. w/ PEO, encephalopathy, ataxia, seizures, neuropathy, hearing loss, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| P163S | 487 c→t (exon 2) | Opthalmoplegia and seizures | Found in trans w/T851A in a 21 y.o. female with peripheral neuropathy, seizures, dysarthria and bilateral ptosis | 1 in 322 mitochondrial disease patients | (Woodbridge et al., 2012) | PubMed |
| E183X | 547 del g (exon 2) | Reference # rs35065786 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=35065786 | PubMed | ||
| R193Q | 578 g→a (exon 2) | Neutral polymorphism | 0.6% of 450 individuals | (GeneSNPs, 2004) | PubMed | |
| Reference # rs3176162 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=3176162 | PubMed | ||||
| C224Y | 671 g→a (exon 3) | Alpers | Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA | (Sarzi et al. 2007) | PubMed | |
| R227W | 679 c→t (exon 3) | PEO | 36% of patients with sporadic PEO with multiple mtDNA deletions carry mutations in one of the three genes associated with familial arPEO or adPEO. Twinkle gene in 7% and POLG1 gene in 25% of our Italian and British patients with sporadic PEO. Found as compound in trans w/ S1176L. Also, found as compound in trans with T251I-P587L. | 7 out of 27patients w/sporadic PEO compared to 250 controls individuals. | (Agostino et al., 2003) | PubMed |
| PEO | Found as compound in trans w/ S1176L. Also, found as compound in trans with T251I-P587L. | (Lamantea and Zeviani, 2004) | PubMed | |||
| Alpers, Severe childhood multi-system disorder | In Alpers found as compound with A467T. In severe childhood multi-system disorder found as compound with D1184N | de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder | (de Vries et al., 2007) | PubMed | ||
| Myopathy and gastrointestinal obstruction | Found in trans w/ G848S with mtDNA depletion and Cox deficient muscle fibers | (Giordano et al., 2009) | PubMed | |||
| R227P | 680 g→c (exon 3) | Severe childhood multi-system disorder | Compound heterozygous with A467T | de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder | (de Vries et al., 2007) | PubMed |
| Epilepsy and failure to thrive | Found in trans w/ A467T | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| R232G | 694 c→g (exon 3) | Infantile Hepatocerebral Syndrome | Found as compound with T251I and P587L | Ferrari et al., 2005 reported 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with an allelic frequency of <0.14% (0 out of 350) in the control group. | (Ferrari et al., 2005) | PubMed |
| Alpers | Found in trans w/ [T251I and P587L] | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Hepatocerebral MDS | Found in trans w/ [T251I andP587L] | (Spinazzola et al., 2009) | PubMed | |||
| R232H | 695 g→a (exon 3) | Liver failure, encephalopathy, and epilepsy | Found as compound in trans with W748S - E1143G | Not found in 200 control alleles | (Kollberg et al., 2006) | PubMed |
| Charcot-Marie Tooth disease, (CMT) (profound cerebellar ataxia) | Found in cis with the S64L SNP and in trans with G737R | Not detected in 282 control alleles | (Harrower et al, 2008) | PubMed | ||
| 697 g→a (exon 3) | Leigh Syndrome | In trans w/G848S | (Taanman et al, 2008) | PubMed | ||
| 695 g→a (exon 3) | Infantile hepatocerebral | Found in trans w/A467T and in cis w/H277L in a 2 mo. mold w/hypotonia, motor paresis and developmentally delayed | (Hunter et al., 2011) | PubMed | ||
| 697 g→a (exon 3) | Infantile hepatocerebral | Found in trans w/A467T and in cis w/H277L in a 1.5 mo. old w/hypotonia and developmentally delayed | (Hunter et al., 2011) | PubMed | ||
| Infantile hepatocerebral | Found W748S and E1143G w/ A467T in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| W235X | 705 g→a (exon 3) | Severe childhood multi-system disorder | Found as compound heterozygote with A467T | de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder | (de Vries et al., 2007) | PubMed |
| Q238R | 713 a→g (exon 3) | Reference # rs56410699 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=56410699 | PubMed | ||
| P241L | 722 c→t (exon 3) | Neutral polymorphism | <1 % in control populations | (Luoma et al., 2007) | PubMed | |
| L244P | 731 t→c (exon 3) | Infantile Hepatocerebral Syndrome | Found as compound with W748S | 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with an allelic frequency of <0.14% (0 out of 350) in the control group. | (Ferrari et al., 2005) | PubMed |
| Alpers | Found 2 infants in trans with W748S | (Spinazzola et al., 2009) | PubMed | |||
| T251I | 752 c→t (exon 3) | PEO | ar PEO. Found as compound with R309L, or 2354G insertion, or G848S in PEO. | 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. | (Ferrari et al., 2005) | PubMed |
| PEO | Found in compound with R807P | (Del Bo et al., 2003) | PubMed | |||
| Infantile Hepatocerebral Syndrome | Frequently found in cis with P587L and compound in trans with L304R, V1106I, and R227W . | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| PEO | Found as compound in trans w/ S1176L, G848S, G785X, V1106I, R309L and R227W and cis w/ P587L. Also, T251I/P587L was found as a homozygous mutation. | (Lamantea and Zeviani, 2004) | PubMed | |||
| PEO and mtDNA deletions | Found in compound w/P587L/ R807P in1 pt. and w/P587L/ H932Y in a 2nd pt. A 3rd pt. was found in compound w/P587L only. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions. | 31 mitochondrial myopathy patients without any family history for the disorder | (Di Fonzo et al., 2003) | PubMed | ||
| Infantile Hepatocerebral Syndrome | 36% of patients with sporadic PEO with multiple mtDNA deletions carry mutations in one of the three genes associated with familial arPEO or adPE. Twinkle gene in 7% and POLG1 gene in 25% of our Italian and British patients with sporadic PEO. Found as compound in trans w/ R227W. Also, found as compound in cis with P587L. | 7 out of 27patients w/sporadic PEO compared to 250 controls individuals. | (Agostino et al., 2003) | PubMed | ||
| MNGIE | Found in cis with P587L and in trans w/N846S. | Van Goethem, 2003: Not found in 280 control chromosomes | ( Van Goethem et al., 2003c) | PubMed | ||
| 754 c→t (exon 3) | Infantile Hepatocerebral Syndrome | Found in 1 of 9 infantile hepatocerebral syndrome patients. In cis with P587L and compound with R232G. | 9 infantile hepatocerebral patients of German and Italian descent. | (Ferrari et al., 2005) | PubMed | |
| PEO | POLG molecular defects were found in 25% of patients with multiple mtDNA deletions and mitochondrial disease. Found in trans w/M603L and in cis with P587L. | 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. | (Gonzalez - Vioque et al., 2006) | PubMed | ||
| PEO | Found in trans w/ G848S and in cis w/ P587L in a 75 y.o. male. | (Kollberg et al., 2005) | PubMed | |||
| Alpers | Found in trans w/ G848S and in cis w/ P587L. Also found in cis w/P587L and in trans w/R853Q in myocerebralhepatopathy patient. Also found as a heterozygous mutation with ataxia, ptosis, and neuropathy. | (Wong et al., 2008) | PubMed | |||
| Alpers | Found in cis w/ R232G and cis w/ P587L. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| PEO | Found in cis w/ P587L, with both mutations on each allele. A 2nd pt. found to have P587L in trans and A467T in cis. | (Stewart et al., 2009) | PubMed | |||
| mtDNA depletion | In cis w/P587L and in trans w/ E1136K | (Taanman et al., 2008) | PubMed | |||
| Hepatocerebral MDS | Found in cis with P587L and in trans with R232G | (Spinazzola et al., 2009) | PubMed | |||
| Restless leg syndrome, ptosis, diplopia, limb weakness, blurred vision | Found in trans with P587L. | (Aitken, et al., 2009) | PubMed | |||
| PEO | Found in trans with W748S andP587L | (Tzoulis, et al., 2009) | PubMed | |||
| PEO and mental retardation | Found in cis w/P587L and in trans w/ R275X | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| PEO, exercise intolerance, diabetes and a 2nd pt. w/ cataract and myopathy | Found in cis w/P587L and in trans w/ A467T | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Ptosis | Found in cis w/P587L and in trans w/ G848S | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Epilepsy and mental retardation | ad, Found w/P587L | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Seizures, hypotonia, and developmental delay | Found w/P587L | (Burusnukul and de los Reyes, 2009) | PubMed | |||
| Acute disseminated encephalomyelitis | Found w/P587L, found in one 4 y.o. patient with autoimmune central nervous system disease | (Harris et al., 2010) | PubMed | |||
| SANDO | Found sporadically w/P587L and G848S in a 80 y.o. male | (Wiess and Saneto, 2010) | PubMed | |||
| Ptosis and myopathy | Found in cis with P587L and in trans with P648R in a 59 y.o. male with dysphagia, dysphonia, myopathy, ptosis, and mtDNA deletions. Father had same symptoms. | (Ferreira et al., 2011) | PubMed | |||
| PEO | Found in cis w/ P587L and in trans w/ H932Y in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Peripheral Neuropathy | Found in cis w/ P587L and in trans w/ H932Y in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in cis w/ P587L and in trans w/ G848S in an 80 y.o. w/ peripheral neuropathy, ptosis, and abnormal muscle histology | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in cis w/ P587L and in trans w/ K1191N in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in cis w/ P587L and in trans w/ N1157S in a 9 y.o. Symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Found in trans w/ G588D and in cis w/ P587L in a 6 y.o. w/ no symptoms noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| G268A | 803 g→c (exon 3) | PEO | Sporadic / unknown Found as compound in trans with A467T | Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians | (Di Fonzo et al., 2003) | PubMed |
| PEO | Sporadic / unknown Found as compound in trans with A467T | (Del Bo et al., 2003) | PubMed | |||
| PEO | Sporadic / unknown Found as compound in trans with A467T | (Baruffini et al., 2006) | PubMed | |||
| PEO | Sporadic / unknown Found as compound in trans with A467T | 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. | (Gonzalez - Vioque et al., 2006) | PubMed | ||
| Parkinsonism, dystonia, mental retardation, hepatocerebral syndrome, ptosis, neuropathy, and intestinal problems | ar, 3 patients ages 3-16 yrs | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Reference # rs61752784 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=61752784 | PubMed | ||||
| R275X | 823 c→t (exon 3) | PEO and mental retardation | Found in trans w/ T251I+P587L | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed |
| R275Q | 824 g→a (exon 3) | Multiple Sclerosis-like illness | Found as a heterozygous mutation w/A467T in a 63 y.o. Pt. first diagnosed w/ optic neuritis and MS 33 yrs earlier. Currently, pt. has ragged-red muscle fibers, ptosis, myopathies, PEO, and mtDNA deletions. | (Echaniz-Laguna et al., 2010) | PubMed | |
| H277L | 830 a→t (exon 3) | Alpers | Found in trans w/T851A | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |
| Infantile hepatocerebral | Found in trans w/A467T and in cis w/R232H in a 2 mo. old w/hypotonia, motor paresis and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Infantile hepatocerebral | Found in trans w/A467T and in cis w/R232H in a 1.5 mo. old w/hypotonia and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Myelopathy,myopathy, peripheral neuropathy and subcortical grey matter degeneration | Found in trans w/A862T in a 66 y.o. female with mtDNA deletions and subcortical grey matter degeneration | (McKelvie et al., 2012) | PubMed | |||
| Y282D | 844 t→g (exon 3) | Alpers | Found in trans w/L304R in a patient with intractable convulsions and severe epileptic status. | 1 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome | (Navarro-Sastre et al., 2012) | PubMed |
| G303R | 907 a→g (exon 4) | Encephalopathy | Found in trans w/ A467T in 2 brothers and a 3rd unrelated pt. All 3 had ataxia, epilepsy, and encephalopathy. | Not found in 170 control individuals | (Tzoulis, et al., 2010) | PubMed |
| Alpers | Found in trans w/ A467T in a pediatric patient w/mitochondrial encelphalomyopathy, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| L304R | 911 t→g (exon 4) | PEO Ataxia - neuropathy | ar Compound in trans with A467T Found as homozygous or compound in trans with W748S - E1143G in SCAE, ataxi-neuropathy | Van Goethem et al., 2001 reported 0 out of 229 control Individuals (<0.4%) | (Van Goethem et al., 2001) | PubMed |
| PEO Ataxia - neuropathy | ar Compound in trans with A467T Found as homozygous or compound in trans with W748S - E1143G in SCAE, ataxi-neuropathy | Not found in 300 healthy French control chromosomes | (Naimi et al., 2006) | PubMed | ||
| PEO Ataxia - neuropathy | ar Compound in trans with A467T Found as homozygous or compound in trans with W748S - E1143G in SCAE, ataxi-neuropathy | ( Stuart et al., 2006) | PubMed | |||
| Alpers | Found homozygous in one pt. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Alpers | Found in trans w/ L392V and R1081dup. | (Cardenas et al., 2010) | PubMed | |||
| VPA induced liver toxicity | Found in trans with A467T in a 15 y.o. pt. with VPA induced hepatotoxicity | Used 968 alleles ethnically matched controls | (Stewart et al., 2010) | PubMed | ||
| Peripheral neuropathy | Found as a homozygote in a 23 y.o. pt. with exercise intolerance, muscle weakness, and ragged red fibers. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ D1145GfsX9 in a developmentally delayed 12 y.o. with seizures and hypotonia. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in trans w/ G737R in a 54 y.o. w/PEO, ptosis, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found as a homozygote in a 12 y.o. w/ PEO, ptosis, neuropathy, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found as a homozygote in a 9 y.o. with PEO, neuropathy, ptosis, and COX deficient fibers. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found as a homozygote in a 2 y.o. pt. w/ encephalopathy, seizures, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in trans w/ A143V in a 22 y.o. pt. with PEO and cerebral cavernous malformation. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found as a homozygote in a 9 y.o. with ptosis, ataxia, hypotonia, and cerebellar atrophy. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found has a homozygote in a 4 y.o. w/ seizures, ptosis, and an abnormal MRI. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found as a homozygote in a 10 y.o. w/ ptosis, PEO, ataxia, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ A467T in a 15 y.o. symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Seizures | Found in trans w/ R1081dup in a 1 y.o. w/seizures and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in trans w/ R1081P in a 10 y.o. w/ ataxia, seizures, PEO, and dystonia | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Alpers | Found in trans w/G888D in a patient showing psychomotor retardation, epileptic encephalopathy, progressive cerebral atrophy, and altered liver enzymes. | 2 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome | (Navarro-Sastre et al., 2012) | PubMed | ||
| Alpers | Found in trans w/Y282D in a patient with intractable convulsions and severe epileptic status. | 2 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome | (Navarro-Sastre et al., 2012) | PubMed | ||
| S305R | 915 c→g (exon 4) | Alpers | heterozygous | (Wong et al., 2008) | PubMed | |
| Alpers | Found in trans w/A467T | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Alpers | Found as a compound heterozygote w/P1073L. | (Baruffini et al., 2011) | PubMed | |||
| Epilepsy and ataxia-neuropathy | Heterozygous mutation w/R627Q found in a 5 y.o. pt. w/epilepsy at age 5, and developed ataxia and neuropathy in his teens. | (Baruffini et al., 2011) | PubMed | |||
| Liver Failure | Found in trans w/ A467T in a 1 y.o. with liver failure | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Alpers | Found in trans w/A467T in a 3 y.o. w/seizures and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Q308H | 924 g→c (exon 4) | PEO | Found in trans w/W748S | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| R309L | 926 g→t (exon 4) | PEO | ar, Compound with T251I | Not found in 100 DNA samples | (Lamantea et al., 2002) | PubMed |
| R309H | 926 g→a (exon 4) | Alpers | Compound in trans with R627Q | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| W312R | 934 t→c (exon 4) | PEO | Found in a 39 y.o. with PEO as a heterozygous mutation | 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG | (Agostino et al., 2003) | PubMed |
| Encephalopathy, dysphagia, and neuropathy | Found in trans with R574W in a 62 y.o. male | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| K319E | 955 a→g (exon 4) | PEO | Found in trans w/ R869Q in a 44 y.o. w/ PEO, ataxia, neuropathy, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| P324S | 970 t→g (exon 4) | Neutral polymorphism | 0.6% of 450 individuals | (GeneSNPs, 2004) | PubMed | |
| Reference # rs2307437 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307437 | PubMed | ||||
| T326fs61X | 975-976 ins c stop@387 (exon 4) | Alpers | Found in trans with A467T | Not found in 300 healthy French control chromosomes | (Naimi et al., 2006) | PubMed |
| S332X | 994 del c or tc→g (exon 4) | Reference # rs35954915 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=35954915 | PubMed | ||
| W347_L356 del | 1039-1068 del (exon 5) | Alpers | 10 amino acid del found in trans w/A467T | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |
| E358A | 1073 a→c del364X (exon 4) | Alpers | Found in trans w/A467T in a 3 y.o. w/seizures, ataxia, and developmentally delayed | (Hunter et al., 2011) | PubMed | |
| 1073 a→c del364X (exon 4) | Alpers | Found in trans w/A467T in a 4 y.o. w/seizures, ataxia, and developmentally delayed | (Hunter et al., 2011) | PubMed | ||
| R374X | 1120 c→t (STOP) (exon 5) | Alpers | Found in trans w/A467T. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |
| G380D | 1139 g→a (exon 5) | PEO | Sporadic mutation found in trans with A467T | Not found in 300 healthy French control chromosomes | (Naimi et al., 2006) | PubMed |
| R386C | 1156 c→t (exon 5) | Isolated distal myopathy of upper limbs and mtDNA depletion | Found as a compound heterozygote w/ H932Y in one 27 y.o. male. Recessive inheritance of both mutated alleles confirmed. | (Giordano et al., 2010) | PubMed | |
| R386H | 1157 g→a (exon 5) | Alpers | Heterozygous single mutation found in a 1 y.o.. | (Baruffini et al., 2011) | PubMed | |
| L392V | 1174 c→g (exon 6) | Neutral polymorphism | Heterozygous with muscle weakness & optic atrophy | <1 % in control populations | (Luoma et al., 2007) (Wong et al., 2008) | PubMed |
| Alpers | Found in cis w/R1081dup and in trans w/L304R | (Cardenas et al., 2010) | PubMed | |||
| R417T | 1250 g→c (exon 6&7 junction) | Alpers | Found in trans w/A467T | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |
| Exon 7 deletion | c.1251-2 a→t (exon 6&7 splice site) | Alpers | Found as a compound heterozygote with A467T. The pt. was a 3.5 y.o. male with VPA induced liver toxicity. | (Schaller et al., 2011) | PubMed | |
| C418R | 1252 t→c (exon 7) | Alpers | Found in trans w/A467T. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |
| Alpers | Found in trans w/A467T in a 43 mo. old female with ataxia and seizures | (McCoy et al., 2011) | PubMed | |||
| L424GfsX28 | 1270-1271 del ct stop @ 452 (exon 7) | PEO | Sporadic / unknown Compound with G431V | 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG | (Agostino et al., 2003) | PubMed |
| Alpers | Found in trans with A467T | (Wong et al., 2008) | PubMed | |||
| G426S | 1276 g→a (exon 7) | Epilepsy, ataxia, myoclonus, cataract, and cognitive delay | ar, found in a 56 yr. old pt. with 2 siblings with epilepsy | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed |
| Seizures | Found in trans w/ G737R in an 11 y.o. w/ seizures and an abnormal MRI | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| L428P | 1283 t→c (exon 7) | Alpers | Found as a heterozygote w/ A467T. | Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation L428P. 19% (9 out of 50) had various mutations in POLG. | (Sarzi et al. 2007) | PubMed |
| M430L | 1288 a→t (exon 7) | PEO with Parkinsonism | ar, Compound (in trans) heterozygous with W918R | Absent in 200 control alleles | (Invernizzi et al., 2008) | PubMed |
| PEO | Found in trans with W918R in a 42 y.o. male with PEO and mtDNA deletions | (Ferreira et al., 2011) | PubMed | |||
| G431V | 1292 g→t (exon 7) | PEO | Sporadic / unknown Compound with L424 CT deletion | 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG | (Agostino et al., 2003) | PubMed |
| S433C | 1298 c→g (exon 7) | PEO- ataxia, peripheral neuropathy | Found in trans with E1143G in a patient with PEO, ataxia, peripheral neuropathy, and episodes of encephalopathy. Mother had heterozygous E1143G variant, but was asymptomatic. | Hudson, 2006: Not detected in 200 controls | (Hudson et al., 2006a) | PubMed |
| PEO | Sporadic, Found in trans with E1143G | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| Q449X | 1345 c→t (exon 7) | Alpers | Found in trans w/ W748S in a 21 y.o. with seizures | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| Y452X | 1356 t→g (exon 7) | PEO | Sporadic | Not detected in 200 controls. | (Hudson et al., 2006a) | PubMed |
| Multiple Sclerosis-like illness | Found as a heterozygous mutation w/T914A in a 56 yr. old. Pt. first diagnosed w/ optic neuritis and MS 19 yrs earlier. Currently has ragged-red muscle fibers, ptosis, myopathies, and mtDNA deletions. | (Echaniz-Laguna et al., 2010) | PubMed | |||
| L463F | 1389 g→t (exon 7) | PEO | ar, Found as compound in trans with S511N | None found in 192 ethnically matched control chromosomes nor in 108 patients with PEO and 140 cases of sporadic PD | (Hudson et al., 2006b) | PubMed |
| A467T | 1399 g→a (exon 7) | PEO | Found as compound with L304R and R3P in PEO. Also found as a homozygous mutation in a PEO pt. | Three out of 229 control individuals were heterozygous for A467T (allele T frequency 0.6%), while the R3P and L304R mutations were not observed. | (Van Goethem et al., 2001) | PubMed |
| PEO | Found as compound with S1104C in a 48 y.o. pt. with PEO | 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG | (Agostino et al., 2003) | PubMed | ||
| PEO | Found in compound with G268A | Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians | (Di Fonzo et al., 2003) | PubMed | ||
| PEO | Found as compound with R627Q, L304R or R3P, or G268A | Van Goethem, 2003: absent in 612 Belgian controls. | (Van Goethem et al., 2003a) | PubMed | ||
| MERRF | homozygous mutation in an 18 y.o. patient w/ myoclonus, seizure, and sensory ataxic neuropathy | (Van Goethem et al., 2003b) | PubMed | |||
| Alpers | Found in compound het with E873stop in Alpers w/ mtDNA depletion | (Naviaux and Nguyen, 2004) | PubMed | |||
| Neurodegenerative disorders and ataxia | Found as a homozygous mutation in 2 of 8 patient w/ ataxia and neurological disorders. Also found in trans with E1143G/W748S in a 2nd patient. | (Van Goethem et al., 2004) | PubMed | |||
| (Chan et al., 2005a) | PubMed | |||||
| Alpers | Studied Alpers pt. fibroblasts with the compound het with E873stop w/ mtDNA depletion. Determined that transcripts containing this stop codon undergo nonsense-associated alternative splicing and nonsense-mediated decay. | (Chan et al., 2005b) | PubMed | |||
| Infantile Hepatocerebral Syndrome | Found as a homozygous mutation in 1 of 9 pts. with progressive neurological and hepatic failure. Also found as in trans w/G848S and a 3rd pt. in trans w/ A957P. Also found in trans with 3482 +2t's splice site variant in a 4th pt. | 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with an allelic frequency of <0.14% (0 out of 350) in the control group. | ( Ferrari et al., 2005) | PubMed | ||
| ataxia-myopathy syndrome | Found as a heterozygous mutation in 4 family members, and found in compound with R627Q in a 5th family member. | ( Luoma et al., 2005) | PubMed | |||
| Alpers | Found in trans w/ W1020X in two infants and also in trans w/ G848S in two other infants. Found as a homozygous mutation in an 8.5 y.o. male. | (Nguyen et al., 2005) | PubMed | |||
| Ataxia Syndrome | Found as a homozygous mutation in 2 members of the same family with mtDNA deletions | (Winterthun et al., 2005) | PubMed | |||
| PEO | Found as a homozygous mutation in a 33 y.o. male with mtDNA deletions | 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. | (Gonzalez-Vioque et al., 2006) | PubMed | ||
| Encephalopathy, liver disorders, and PEO | A467T is common in children, but complete POLG1 sequencing is required to identify multiple mutations that can have complex implications for genetic counseling. Studied a large collection of patients with clinical, biochemical and molecular genetic evidence of mitochondrial disease from several European research clinics. Found as compound in trans with K1191N, G848S, T914P, c. 2480+1g>a, E1143G + Q879H, 3482+2t>c, W748S, E1143G, and R627W.. Found as homozygous mutation in4 patients. | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| Oxidative phosphorylation enzyme complex deficiencies | Found as a homozygous mutation in 1 of 8 patients. Also found in trans w/ R227W, R227P, W235X, G848S, and A957P. | de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder | (de Vries et al., 2007) | PubMed | ||
| Liver failure, encephalopathy, and epilepsy | Found in trans w/ R574W, G848S, W748S in children w/ progressive encephalopathy. | Not found in 200 control alleles | (Kollberg et al., 2006) | PubMed | ||
| Alpers | Found in trans w/ T914P, T326fsX38, and G380D | Not found in 300 healthy French control chromosomes | (Naimi et al., 2006) | PubMed | ||
| Epilepsy, PEO, and ataxia | Found as a homozygous mutation in 5 mitochondrial disease pts. Also, found in trans w/W748S in 6 pts. with mitochondrial disease. | Studied in 26 mitochondrial disease patients | (Tzoulis et al., 2006) | PubMed | ||
| PEO | Identified a diverse range of phenotypes arising from PEO-associated amino acid substitutions introduced in the yeast pol gamma gene. | (Stuart et al., 2006) | PubMed | |||
| Alpers | Found as a heterozygote mutation with L428P. | Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation L428P. 19% (9 out of 50) had various mutations in POLG. | (Sarzi et al., 2007) | PubMed | ||
| Alpers w/ valporate induced hepatic failure | Found in cis w/T885s and in trans w/Q879H and E1143G. | (McFarland et al., 2008) | PubMed | |||
| Alpers, Ataxia Neuropathy, and arPEO+ | Found in trans w/ L886P, Q68X, Q715X, T849H, T914P, L83P, G888S, R1138C, c.2480+1, c. 2157+5, G737R, and L424G | (Wong et al., 2008) | PubMed | |||
| Alpers | Found in trans w/ [R852C and G11D], and, found in trans w/ T914P in 2 additional pts. In trans w/E873X. In trans w/ W347_L356 del. In trans w/G848S. In trans w/L966R. In trans w/R374X. In trans w/ R417T. In trans w/C418R. One pt., found as a homozygous mutation. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Alpers, PEO | Found in trans w/L605R, and in a 2nd pt. in trans w/ W748S. Also, found as a homozygous mutation. Found in trans w/ T251I and P587L. Also found in trans w/ G11D and R852C. Also found in trans w/G848S. | (Stewart et al., 2009) | PubMed | |||
| Alpers | Found in trans w/T914P | (Taanman et al., 2008) | PubMed | |||
| Alpers | Found in trans w/ R574W | (Spinazzola et al., 2009) | PubMed | |||
| Alpers | Homozygous | (Spinazzola et al., 2009) | PubMed | |||
| Alpers | Found in trans w/ splice variant c.3643 +2t>c | (Roels, et al., 2009) | PubMed | |||
| mtDNA depletion | Found in trans w/ G8484S. | (Roels, et al., 2009) | PubMed | |||
| Prematurity, epilepsy, deafness, retinitis pigmentosa, hemiparesis, and liver failure | Found in trans w/ K925RfsX42 | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Alpers | 5 patients found with a homozygous mutation | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Epilepsy and failure to thrive | Found in trans w/ R227P | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| PEO, exercise intolerance, diabetes, and a 2nd pt. w/ cataract and myopathy | 2 patients; found in trans w/ T251I + P587L | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Alpers | Found in trans w/S305R | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| PEO, ptosis, polyneuropathy, ataxia, and dysarthria | Found in trans w/ W748S and in compound w/ E1143G | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Epilepsy, myoclonus, polyneuropathy, ataxia, and cognitive delay; a 2nd pt. with epilepsy and MELAS-like symptoms | Found in trans w/ W748S | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Epilepsy, myoclonus, and developmental delay | Found in trans w/T914P | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Epilepsy, liver failure, occipital strokes, and growth retardation | Found in trans w/ A957P | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Spinocerebellar ataxia, neruo-degeneration, and impaired cognitive functions | ar, 2 patients ages 19 and 48 | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Epilepsy and myoclonus | ar, found with E1143G | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Found with W748S in a 43 yr. old patient | (Schulte et al., 2009) | PubMed | |||
| Cerebellar ataxia, sensory neuropathy, and dysphagia | Homozygous. Found in 2 early 20 yr. old sisters, and only one with epilepsy | (Schulte et al., 2009) | PubMed | |||
| SANDO | Homozygous. Found in 2 siblings in their mid 40's. mtDNA deletions and COX1 deficient fibers in muscle biopsies | (McHugh et al., 2010) | PubMed | |||
| Alpers | Found in trans with G848S | (Hasselmann et al., 2009) | PubMed | |||
| Hepatocerebral - Alpers symptoms | Found in trans w/P1073L in 2 pt., Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility. | (Kurt et al., 2010) | PubMed | |||
| Encephalopathy | Found in trans w/ G303R in 2 brothers and a 3rd unrelated pt. All 3 had ataxia, epilepsy, and encephalopathy. | Not found in 170 control individuals | (Tzoulis et al., 2010) | PubMed | ||
| SANDO | Found in trans with W748S+E1143G. Sensory ataxia, dysarthria, and opthalmoplegia. | (Posada et al., 2010) | PubMed | |||
| Alpers | Found as a compound heterozygote w/ a 4.7 kb POLG deletion from intron 14 thru intron 21 w/ a CGH array. Patient had early on set of Alpers and died at the age of 3.5 y.o.. The father carried the A467T mutation, and the mother the deletion. | (Compton et al., 2010 and Tang et al., 2011) | PubMed | |||
| Multiple Sclerosis-like illness | Found as a heterozygous mutation w/R275Q in a 63 yr. old. Pt. first diagnosed w/ optic neuritis and MS 33 yrs earlier. Currently, pt. has ragged-red muscle fibers, ptosis, myopathies, PEO, and mtDNA deletions. | (Echaniz-Laguna et al., 2010) | PubMed | |||
| Alpers | Found in trans w/ P625R in a 1 y.o. with epilepsy and liver failure. | (Baruffini et al., 2011) | PubMed | |||
| Epilepsy | Found heterozygous with T 914P in a 10 mo. old male with myoclonic seizures and jerks, and developmental regression. | (Dhamija et al., 2011) | PubMed | |||
| Alpers | Found in trans with E1143G, Q497H and W748S in a 6 y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Alpers | Found in trans with T914P in a 9 mo. old with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| VPA induced liver toxicity | Found in trans with L304R in a 15 y.o. pt. with VPA induced hepatotoxicity | Used 968 alleles ethnically matched controls | (Stewart et al., 2010) | PubMed | ||
| Alpers | Found as a compound heterozygote with the splice site mutation c.1251-2a→t resulting in the deletion of exon 7. The pt. was a 3.5 y.o. male with VPA induced liver toxicity | (Schaller et al., 2011) | PubMed | |||
| Encephalopathy | Found in trans with Q715X in a 5 y.o. pt. | 2697 patients with clinical suggestive presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Liver Diseases | Compound heterozygote in cis with W748S | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ T914P in a 3 y.o. with hypotonia, encephalopathy, seizures, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ G848S in an 8 y.o. pt. with seizures, muscle weakness, hypotonia, ataxia, hearing loss, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ G848S in a 1 y.o. pt. with seizures and elevated transaminases, and increased signal basal ganglia | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| SANDO AND PEO | Found in trans w/ W748S in a 54 y.o. with PEO, ptosis, ataxia, neuropathy, and SANDO | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ W748S in a 16 y.o. with seizures, dystonia, choria, neuropathy, and ptosis | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Encephalopathy and ataxia | Found in trans w/ R597W in a 26 y.o. with encephalopathy, ataxis, ptosis, and neuropathy | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/K1050RfsX44 in a 4 y.o. w/ seizures, ataxia, hypotonia, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found as a homozygote in a 46 y.o. pt. w/ ptosis, neuropathy, muscle weakness, and ataxia | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/W748S in an 18 y.o. with ataxia, seizures, dystonia, and optic atrophy. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Ataxia | Found as a homozygote in a 48 y.o. w/ hypotonia, ataxia muscle weakness, and headaches. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in a 2 y.o. w/ hypotonia, encephalopathy, seizures, cardiomyopathy, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found as a homozygote in a 19 y.o. w/ ataxia, myoclonic seizures, optic atrophy, dysarthria, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO and seizures | Found as a homozygote in a 40 y.o. w/ PEO, ataxia, seizures, and neuropathy | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ L1113P in a 1 y.o. with encephalopathy, seizures, and hepatic failure | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ T914P in a 5 y.o. w/ seizures, hearing loss, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Liver failure | Found in trans w/ S305R in a 1 y.o. with liver failure | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures and liver failure | Found in trans w/ R852C and G11D in a 8 mo. w/ seizures, liver failure, and lactic acidosis. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ F749S in a 6 y.o. w/ seizures | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Hepatic failure | Found in trans w/ S1095R in a 6 mo. w/ hypotonia, liver failure, abnormal muscle histology, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ T914P in a 9 mo. w/ seizures, hypotonia, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures and hepatic failure | Found in trans w/ T914P in a 4 y.o. with liver failure, seizures, and failure to thrive | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ Q1024X in a 2y.o. w/seizures, hearing loss, and hemiparesis | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ W748S in a 29 y.o. symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| PEO | Found in trans w/ A143V in a 49 y.o. w/ PEO, encephalopathy, ataxia, seizures, neuropathy, hearing loss, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ L304R in a 15 y.o. Symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Liver failure | Found in trans w/ R807C in a 1 y.o. w/ encephalopathy, liver failure, and lactic acidosis | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ T914P in an 8 mo. w/ seizures, respiratory failure, and an abnormal MRI | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ F749S in an 8 mo. symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Seizures and hepatic failure | Found in trans w/ H754Q in a 2 y.o. w/ seizures, hepatic failure, and cerebellar atrophy. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ C1188R in a 3 y.o. w/ seizures, hypotonia, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| VPA induced liver failure | Found in trans w/ G588D in a 2 y.o. w/ VPA induced liver failure | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ F88L in a 42 y.o. w/ no symptoms noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Alpers | Found in trans w/G848S in a 3 y.o. w/seizures, developmentally delayed, and ataxia | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/G848S in a 11 mo. old w/seizures and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found as a homozygous mutation in a 10 y.o. w/seizures and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/IVS14+1G>A in a 2 y.o. w/seizures, developmentally delayed, and ataxia | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/R852C in a 5 y.o. w/seizures, ataxia, and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/S305R in a 3 y.o. w/seizures and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/L966R in a 1 y.o. w/ seizures and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/E358A del364X in a 3 y.o. w/seizures, ataxia, and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/E358A del364X in a 4 y.o. w/seizures, ataxia, and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/L966R in a 1 y.o. w/ seizures and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Infantile hepatocerebral | Found in trans w/R232H and H277L in a 2 mo. old w/hypotonia, motor paresis and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Infantile hepatocerebral | Found in trans w/R232H and H277L in a 1.5 mo. old w/hypotonia and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/ R574W in 2 pediatric patients w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| Alpers | Found in trans w/ G848S in a pediatric patient w/mitochondrial encelphalomyopaty, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| Alpers | Found in trans w/ G303R in a pediatric patient w/mitochondrial encelphalomyopaty, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| Alpers | Found in trans w/L966R in a 17 mo. old male with seizures and encephalopathy | (McCoy et al., 2011) | PubMed | |||
| Alpers | Found in trans w/G848S in a 10 mo. old female with seizures and brain stem dysfunction. History revealed that a 24 y.o. cousin died from Alpers whom harbored a homozygous A467T variant. | (McCoy et al., 2011) | PubMed | |||
| Alpers | Found in trans w/R852C in a 21 mo. old female with blindness, anarthria, hypotonia, and epilepsy | (McCoy et al., 2011) | PubMed | |||
| Alpers | Found in trans w/C418R in a 43 mo. old female with ataxia and seizures | (McCoy et al., 2011) | PubMed | |||
| Alpers to Leigh's encephalopathy | Found in trans w/G848S in a 3.5 mo. old female with seizures and Alpers. Post mortem studies revealed Leigh's encephalopathy | (Scalais et al., 2012) | PubMed | |||
| MNGIE-like | Found as a homozygous mutation in a 46 y.o. male with PEO, ptosis, exercise intolerance, peripheral neuropathy, ataxia, and hearing loss | (Tang et al., 2012) | PubMed | |||
| Torticollis and PEO | Found in trans w/W748S in a 43 y.o. female with abnormal gait, ataxia, PEO, and head jerks. | (Tuladhar et al., 2012) | PubMed | |||
| Parieto-occipital lobe epilepsy | Found in trans w/ W748S in a 16 y.o. female with seizures, headaches, cerebellar ataxia, axonal neuropathy, visual impairment, and impaired cognitive function | (Roshal et al., 2011) | PubMed | |||
| PEO | Found in trans w/W748S in a 24 y.o. female with arPEO, cerebellar ataxia, and mtDNA deletions | (Lax et al., 2012b) | PubMed | |||
| PEO | Found in trans w/X1240Q in a 59 y.o. male with arPEO and sensory neuropathy | (Lax et al., 2012b) | PubMed | |||
| PEO | Found in trans w/X1240Q in a 59 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| PEO | Found in trans w/X1240Y in a 42 y.o. Female with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| PEO | Found as a homozygous mutation in a 36 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| PEO | Found in trans w/W748S in a 47 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| PEO | Found in trans w/X1240Y in a 42 y.o. female with PEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| PEO | Found as a homozygous mutation in a 44 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| PEO | Found in trans w/W748S in a 48 y.o. male with PEO, ptosis, ataxia and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| Epilepsy | Found in trans w/W748S in a 18 y.o. female with epilepsy, ataxia and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| Epilepsy | Found in trans w/W748S in a 20 y.o.female with epilepsy, ataxia and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| N468D | 1402 a→g (exon 7) | PEO | Found in compound w/A1105T in a family w/PEO | Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes. | (Luoma et al., 2004) | PubMed |
| PEO | Found in trans w/A1105T in 3 family members w/ PEO | (Wanrooij et al., 2004) | PubMed | |||
| Microcephaly, cerebellar atrophy, hypotonia, and retinitis pigmentosa | Found as a heterozygous mutation in a 15 y.o. female w/ progressive cerebellar atrophy, hypotonia, and retinitis pigmentosa. | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Sensory neuropathy and PEO | Heterozygous. Found in 3 related patients. A father with PEO, and a son with cerebellar ataxia and dysphagia, and the father's sister with PEO only | (Schulte et al., 2009) | PubMed | |||
| Opthmalplegia and peripheral neuropathy | Found in trans w/T851A in a 49 y.o. female with ptosis, lower limb weakness, sensory ataxia, gastrointestinal symptoms, and peripheral neuropathy | 1 in 322 mitochondrial disease patients | (Woodbridge et al., 2012) | PubMed | ||
| c. 1433 +1g→a | 1433 ins g→a (Splice variant between ex 7 and ex 8) | Seizures | Found in trans w/ A467T in a 2 y.o. w/ hypotonia, encephalopathy, seizures, cardiomyopathy, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| Y479X | 1433 large del (exon 8) | Reference # rs71653298 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=71653298 | PubMed | ||
| Q497H | 1491 g→c (exon 8) | Ataxia Syndrome | Found allelic (cis) with W748S + E1143G | 1 in 97 found in healthy controls and 1 in 99 found mtDNA disease patients | (Winterthun et al., 2005) | PubMed |
| Alpers, Ataxia Neuropathy | In cis with W748S-E1143G. Also found in trans w/G848S, and also in trans w/A467T. | (Wong et al., 2008) | PubMed | |||
| Alpers | In cis w/ W748S and E1143G, and in trans w/ G848S. | Found in one child w/ a normal brain MRI | (Brunetti-Pierri et al., 2008) | PubMed | ||
| Alpers | Found in cis with E1143G and W748S, and in trans with A467T in a 6 y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| S511N | 1532 g→a (exon 8) | PEO | ad | None found in 192 ethnically matched control chromosomes nor in 108 patients with PEO and 140 cases of sporadic PD | (Hudson et al., 2006b) | PubMed |
| G517V | 1550 g→t (exon 8) | Ataxia - neuropathy | Found in trans w/ E1143G in a father and his 8 y.o. daughter w/ exercise intolerance, ataxia, and neuropathy. | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| Leigh Syndrome | Found as a heterozygous mutation in a female pt. w/ dominant ataxia and neuropathy | Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation L428P. 19% (9 out of 50) had various mutations in POLG. | (Sarzi et al., 2007) | PubMed | ||
| Myopathy and micro-cephaly | Found in trans w/ D1196N and R1128H | (Wong et al., 2008) | PubMed | |||
| adPEO | Heterozygous, short-stature, Leigh-like disease, neuropathy, stroke, dystonia, chorea, diabetes, myoclonus, Sideroblastic anemia, splenmegaly, Pearson Syndrome to KSS | (Wong et al., 2008) | PubMed | |||
| Myoclonic epilepsy | In trans w/R722H, and in association w/ a mutation in SCN1A, R1645Q | (Bolszak et al., 2009) | PubMed | |||
| Cerebellar ataxia, dystonia, epilepsy, PEO, hypotonia, mental retardation, and chorea | ad, 4 patients ages 4-40 yrs. | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Seizures, hypoglycemia, myoclonus, hypotonia, and developmental delay | Heterozygous, found in 2 half siblings and their unaffected mother | (Burusnukul and de los Reyes, 2009) | PubMed | |||
| Cerebellar ataxia, PEO, and dysphagia | Heterozygous. Found in a 44 yr. old patient | (Schulte et al., 2009) | PubMed | |||
| Diabetes, strokes, psychosis, and epilepsy | Heterozygous. Ad, found in twins, their mother, and grandmother | (Hopkins et al., 2009) | PubMed | |||
| PEO | 56 y.o. male with a heterozygous mutation, and ptosis, myopathy, neuropathy, and mtDNA deletions. | (Ferreira et al., 2011) | PubMed | |||
| PEO | Found as a heterozygous mutation in a 33 y.o. female with PEO and mtDNA deletions. Father also affected. | (Ferreira et al., 2011) | PubMed | |||
| PEO | Found in cis w/ Y955C in a 47 y.o. w/ PEO, ptosis, myopathy, and neuropathy | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures and mitochondrial myopathy | Found as a heterozygous mutation in a 56 y.o. woman with mitochondrial myopathy, seizrues, ataxia, dysarthria, and dysphonia | 1 in 322 mitochondrial disease patients | (Woodbridge et al., 2012) | PubMed | ||
| Neuronal ceroid lipofuscinosis | Maternally inherited heterozygous mutation found with a mutation in CLN5. Infant with hypotonia, bilateral ptosis, and diffuse cerebral atrophy. A 45% reduction in mtDNA compared to controls. | (Staropoli et al., 2012) | PubMed | |||
| Neutral polymorphism | Biochmeical analysis of the recombinant Pol gamma with G517V revealed wild type activity | (Kasiviswanathan and Copeland, 2011) | PubMed | |||
| R546C | 1636 c→t (exon 9) | Neutral polymorphism | 1% | 1.1% of 450 individuals | (GeneSNPs, 2004) | PubMed |
| Heterozygous with R628Q in one breast tumor | (Singh et al, 2009) | PubMed | ||||
| Reference # rs2307447 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307447 | PubMed | ||||
| R546S | 1636 c→a (exon 9) | Reference # rs2307447 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307447 | PubMed | ||
| R546G | 1636 c→g (exon 9) | Reference # rs2307447 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307447 | PubMed | ||
| K561M | 1882 a→t (exon 9) | Dysmorphy, hypotonia, coloboma, heart failure, and liver insufficiency | Compound heterozygosity in cis with W748S | Sarzi et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation K561M in cis with W748S. | (Sarzi et al., 2007) | PubMed |
| R562Q | 1685 g→a (exon 9) | PEO | sporadic | Not found in 100 DNA samples from healthy Italians | (Di Fonzo et al., 2003) | PubMed |
| H569Q | 1707 c→(a or g) (exon 9) | Homozygous | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | ||
| R574W | 1720 c→t (exon 10) | PEO | Found in trans w/ W312R in a 37 y.o. male patient w/ PEO, dysphagia, and myopathy. | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| Liver failure, encephalopathy, and epilepsy | Found in trans w/A467T in 2 family members whose parent are unaffected heterozygotes. | Kollberg, 2006: Not found in 200 control alleles | (Kollberg et al., 2006) | PubMed | ||
| Alpers | Found in trans w/ A467T | (Spinazzola et al., 2009) | PubMed | |||
| Alpers | Found in trans w/ A467T in 2 pediatric patients w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| R579W | 1735 c→t (exon 10) | PEO | Sporadic / unknown Compound with A889T | Not detected in 120 healthy control alleles | (Filosto et al., 2003) | PubMed |
| W585X | 1754 g→a (exon 10) | PEO | Found in trans with P648R in a 50 y.o. male with PEO, dysphagia, dysphonia, and parkinsonism with mtDNA deletions | (Ferreira et al., 2011) | PubMed | |
| P587L | 1760 c→t (exon 10) | PEO, neuropathy, and hearing loss | Found in trans w/ Q1236H in 2 different families and affected siblings | Filosto, 2003: not detected in 120 healthy control alleles. | (Filosto et al., 2003) | PubMed |
| PEO and mtDNA deletions | Found in compound w/T251I/ R807P in1 pt. and w/T251I/ H932Y in a 2nd pt. A 3rd pt. was found in compound w/T251 only. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions. | Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians. | (Di Fonzo et al., 2003) | PubMed | ||
| PEO | Found in compound w/T251I and N864S in 2 sisters. | Van Goethem, 2003: Not found in 280 control chromosomes. | (Van Goethem et al., 2003c) | PubMed | ||
| Infantile Hepatocerebral Syndrome | Found in compound w/T251I and R232G | Ferrari et al., 2005 reported 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. | (Ferrari et al., 2005) | PubMed | ||
| PEO | Found in compound w/T251I and G8484S in a 75 y.o. male | (Kollberg et al., 2005) | PubMed | |||
| PEO | Found as compound in trans w/ S1176L, G848S, G785X, V1106I, R309L and R227W and cis w/ T251I. Also, T251I/P587L was found as a homozygous mutation. | (Lamantea and Zeviani, 2004) | PubMed | |||
| PEO | Found in cis w/T251I and trans w/M603L. Also found in trans w/ R853W (no T251I). All had mtDNA deletions. | 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. | (Gonzalez-Vioque et al., 2006) | PubMed | ||
| Alpers | Found in cis w/ T251I and in trans w/ G848S, also found as a hetero. mutation with ataxia, ptosis, and neuropathy | (Wong et al., 2008) | PubMed | |||
| Alpers | Found in trans w/R232G and in cis w/T251I. Also, in cis w/P589L and in trans w/W748S. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Alpers | Found in cis with T251I with both mutations on each allele. Also, found in cis w/A467T and in trans w/T251I. | (Stewart et al., 2009) | PubMed | |||
| mtDNA depletion | In cis w/T251I and in trans w/E1136K | (Taanman et al., 2008) | PubMed | |||
| Hepatocerebral MDS | Found in cis w/ T251I and in trans w/ R232G | (Spinazzola et al., 2009) | PubMed | |||
| Restless leg syndrome, ptosis, diplopia, limb weakness, blurred vision | Found in trans with T251I. | (Aitken, et al., 2009) | PubMed | |||
| PEO | Found in cis with W748S and in trans with T251I. | (Tzoulis, et al., 2009) | PubMed | |||
| PEO and mental retardation | Found in cis w/ T251I and in trans w/ R275X | >0.5% of Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| PEO, exercise intolerance, diabetes and a 2nd pt. w/ cataract and myopathy | Found in cis w/T251I and in trans w/A467T | >0.5% of Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Ptosis | Found in cis w/T251I and in trans w/G848S | >0.5% of Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| PEO, ptosis, epilepsy, mental retardation, ataxia, polyneuropathy, and cataract | Ad, in cis w/T251I 3 patients: 4 yr. old w/PEO, ptosis, and motor delay development. A 10 yr. old with epilepsy and mental retardation, and 44 yr. old w/ cataract, polyneuropathy, myopathy, and ataxia | >0.5% of Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Seizures, hypotonia, and developmental delay | Found w/T251I | (Burusnukul and de los Reyes, 2009) | PubMed | |||
| Acute disseminated encephalomyelitis | Found w/T251I, found in one 4 yr. old patient with autoimmune central nervous system disease | (Harris et al., 2010) | PubMed | |||
| SANDO | Found sporadically w/T251I and G848S in a 80 yr. old male | (Weiss and Saneto, 2010) | PubMed | |||
| Ptosis and myopathy | Found in cis with T251I and in trans with P648R in a 59 y.o. male with dysphagia, dysphonia, myopathy, ptosis, and mtDNA deletions. Father had same symptoms. | (Ferreira et al., 2011) | PubMed | |||
| PEO | Found in cis w/ T251I and in trans w/ H932Y in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Peripheral Neuropathy | Found in cis w/ T251I and in trans w/ H932Y in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in cis w/ T251I and in trans w/ G848S in an 80 y.o. w/ peripheral neuropathy, ptosis, and abnormal muscle histology. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in cis w/ T251I and in trans w/ K1191N in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in cis w/ T251I and in trans w/ N1157S in a 9 y.o. Symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Found in trans w/ G588D and in cis w/ T251I in a 6 y.o. w/ no symptoms noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| G588D | 1763 g→a (exon 10) | VPA induced liver failure | Found in trans w/ A467T in a 2 y.o. w/ VPA induced liver failure | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| Found in trans w/ T251I and P587L in a 6 y.o. w/ no symptoms noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| P589L | 1766 c→t (exon 10) | Alpers | Found in cis w/P587L and in trans w/W748S. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |
| L591F | 1774c→t (exon 10) | SANDO | Found in trans w/R1096C in a 48 y.o. female with SANDO and dysphagia. | (Kurt et al., 2012) | PubMed | |
| R597W | 1789 c→t (exon 10) | PEO with ataxia | Homozygous | (Stewart et al., 2009) | PubMed | |
| PEO, seizures, and VPA induced liver failure | Found as a homozygote in an 18 y.o. with PEO, neuropathy, seizures, and VPA induced hepatotoxicity | 2697 patients with clinical suggestive presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Encephalopathy and ataxia | Found in trans w/ A467T in a 26 y.o. w/ encephalopathy, ataxia, neuropathy, and ptosis. | 2697 patients with clinical suggestive presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| M603L | 1807 a→t (exon 10) | PEO with ptosis | Found as compound in trans with T251I-P587L | 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. | (Gonzalez-Vioque et al., 2006) | PubMed |
| L605R | 1814_1815 tt→gc (exon 10) | Alpers | Found in trans w/ A467T. Mitochondria depletion in liver | (Stewart et al., 2009) | PubMed | |
| Y614X | 1842 c→ a or g | Reference # rs62640033 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640033 | PubMed | ||
| R617C | 1849 c→t (exon 10) | Heterozygous with muscle weakness, exercise intolerance, hearing loss, arrhythmia | (Wong et al., 2008) | PubMed | ||
| L623W | 1868 t→g (exon 10) | Hypoketotic, hypyoglycaemial, and liver dysfunction | Compound heterozygote w/ K755E | Not found in 200 healthy controls | (Bortot, et al., 2009) | PubMed |
| P625R | 1874 c→g (exon 10) | Alpers | Found as a compound heterozygote w/ A467T in a 1 y.o. with epilepsy and liver failure. | (Baruffini et al., 2011) | PubMed | |
| R627W | 1879 c→t (exon 10) | PEO | Found in trans w/A467T in a 39 y.o. male whose unaffected parents are hets for each mutation. | Van Goethem, 2003: absent in 612 Belgian controls. | (Van Goethem et al., 2003a) | PubMed |
| PEO | Found in trans w/ A467T in 2 PEO patients w/ hearing loss | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| Alpers | Found in trans w/T914P | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| R627Q | 1880 g→a (exon 10) | Ataxia - myopathy PEO - ataxia - neuropathy Alpers | Found in cis with Q1236H and in trans with A467T Found in compound in trans with R309H or R1096H in Alpers Found in cis with Q1236H and in trans with L965stop-E1143G in PEO | (Luoma et al., 2005) | PubMed | |
| Ataxia - myopathy PEO - ataxia - neuropathy Alpers | Found in cis with Q1236H and in trans with A467T Found in compound in trans with R309H or R1096H in Alpers Found in cis with Q1236H and in trans with L965stop-E1143G in PEO | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| MELAS | Found w/ G848S; heterozygous mutation; w/ mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. | (Deschauer et al., 2007) | PubMed | |||
| Ataxia Neuropathy | Found in cis w/ G11D and in trans w/ R852C. | (Wong et al., 2008) | PubMed | |||
| Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Found with G848S in a 35 yr. old patient | (Schulte et al., 2009) | PubMed | |||
| Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Found with T1199X ins. a at c.3594 in a 47 yr. old patient | (Schulte et al., 2009) | PubMed | |||
| Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Found with R1096C in a 43 yr. old patient | (Schulte et al., 2009) | PubMed | |||
| Epilepsy and ataxia-neuropathy | Found as a compound heterozygote w/S305R in a 5 y.o. with epilepsy that developed ataxia and neuropathy in his teens. | (Baruffini et al., 2011) | PubMed | |||
| Encephalopathy | Found in trans w/ R852C and G11D in a 25 y.o. w/ dementia, encephalopathy, and stroke. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| R628Q | 1883 g→a (exon 10) | Mutation found in one breast tumor heterozygous w/ the SNP R546C | (Singh et al., 2009) | PubMed | ||
| P648R | 1943 c→g (exon 10) | SANDO | Found in compound w/R807C in a 39 y.o. patient. | (Gago et al., 2006) | PubMed | |
| PEO + myopathy | ar, Found as either homozygous mutation or as compound in trans with R1096C in PEO. | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| Ptosis and myopathy | Found in trans with T251I and P587L in a 59 y.o. male with dysphagia, dysphonia, myopathy, ptosis, and mtDNA deletions. Father had same symptoms. | (Ferreira et al., 2011) | PubMed | |||
| SANDO | Found in trans with R807C in a 49 y.o. pt. with SANDO and mtDNA deletions | (Ferreira et al., 2011) | PubMed | |||
| PEO | Found in trans with W585X in a 50 y.o. male with PEO, dysphagia, dysphonia, and parkinsonism with mtDNA deletions | (Ferreira et al., 2011) | PubMed | |||
| H659Q | 1977 c→g (exon 11) | Reference # rs62640030 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640030 | PubMed | ||
| E662K | 1984 g→a (exon 11) | Neutral polymorphism | 2.8% of 450 individuals | (GeneSNPs, 2004) | PubMed | |
| Q666L | 1997 a→t (exon 11) | Reference # rs62640029 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640029 | PubMed | ||
| R709X | 2125 c→t (exon 12) | PEO | Found as compound with T251I. | (Del Bo et al., 2003) | PubMed | |
| PEO | Found as compound with T251I-P587L in a pt. w/ mtDNA deletions. | Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians | (Di Fonzo et al., 2003) | PubMed | ||
| Q715X | 2143 c→t (exon 12) | Alpers | Found in trans w/ A467T | (Wong et al., 2008) | PubMed | |
| Encephalopathy | Found in trans w/ A467T in a 5 y.o. pt. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| c.2157+5_+6gc>ag | 2157 gc→ ag (exon 12) | Alpers | Found in trans with A467T, most likely a splice site mutation. | (Wong et al., 2008) | PubMed | |
| R722H | 2165 g→a (exon 13) | Neutral polymorphism | <1 % in control populations | (Luoma et al., 2007) | PubMed | |
| Myoclonic epilepsy | (Bolszak et al., 2009) | PubMed | ||||
| PEO, mtDNA deletions and neurological phenotypes | Homozygous in 3 siblings with mtDNA deletions, hearing loss, diabetes, dementia, dysphagia, and limb myopathy. Also found in trans w/ W748S in two siblings w/ ptosis, epilepsy, mental retardation | 1:135 carrier frequency in a Finnish population | (Komulainen et al., 2010) | PubMed | ||
| Alpers | Found in trans with V1044A in a 2.5 y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| H734R | 2201 a→g (exon 13) | Reference # rs56119329 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=56119329 | PubMed | ||
| N736S | 2207 a→g (exon 13) | Ataxia, cardiomyopathy, and depression | Found in a 52 y.o. female with melancholic depression, unstable gailt, and dilated cardiomyopathy. | (Verhoeven et al., 2011) | PubMed | |
| G737R | 2209 g→c (exon 13) | Epilepsy and liver failure | Found as compound in trans with A767D in two family members | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| Parkinsonism | Parkinsonism in trans with R853W. | (Davidzon et al., 2006) | PubMed | |||
| 2210 g→c (exon 13) | Charcot-Marie Tooth disease, (CMT) (profound cerebellar ataxia) | Found in trans with the S64L-R232H in CMT. | Found in 2/666 (0.3%) of control alleles | (Harrower et al, 2008) | PubMed | |
| arPEO+ and Myocerebrohepatopathy (MCHS) | Found in trans w/ A467T. In trans w/ E1143G-R943C in MCHS. Also, found as a single heterozygous mutation. | (Wong et al., 2008) | PubMed | |||
| PEO | Found in trans with W748S. | (Tzoulis, et al., 2009) | PubMed | |||
| PEO | Found in trans w/ L304R in a 54 y.o. with PEO, ptosis, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ G426S in an 11 y.o. w/ seizures and an abnormal MRI | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ V855L in an 8 mo. w/ seizures, liver failure, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans A957V in a 4 mo. No symptoms noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| N740D | 2218 a→g (exon 13) | Reference # rs78347903 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=78347903 | PubMed | ||
| V742M | 2224 g→a (exon 13) | SNP | Reference # rs147827654 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusID=5428 | PubMed | |
| G746S | 2236 g→a (exon 13) | Ataxia, PEO | ar, Found in cis w/ E1143G, and in trans G848S | 1in 454 alleles | (Stewart et al., 2009) | PubMed |
| PEO | Found in trans w/G848S in a 36 y.o. male with PEO, peripheral neuropathy, and ataxia | (Lax et al., 2012a) | PubMed | |||
| W748S | 2243 g→c (exon 13) | Ataxia | Found in compound w/E1143G w/ataxia, dysarthria, and cognitive impairment. Also found as a homozygous mutation. | (Van Goethem et al., 2004) | PubMed | |
| Infantile Hepatocerebral Syndrome | Found in trans w/ Y1210fs1216X and also in trans w/ L244P | Ferrari et al., 2005 reported 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. | (Ferrari et al., 2005) | PubMed | ||
| Hepatocerebral Syndrome | Found in 4 children in cis w/E1143G and in trans w/G8484S. | (Davidzon et al., 2005) | PubMed | |||
| Ataxia | Found as a homozygous mutation w/ E1143G | Carrier frequency in the general Finnish population of 1:125 from 500 control chromosomes | (Hakonen et al., 2005) | PubMed | ||
| Alpers | Found in trans w/E1143G and in cis w/G848S in a 13 mo. old male | (Nguyen et al., 2005) | PubMed | |||
| Ataxia Syndrome | Found in trans w/Q497H in patients w/ progressive ataxia and epilepsy | 1 in 97 found in healthy controls and 1 in 99 found mtDNA disease patients | (Winterthun et al., 2005) | PubMed | ||
| PEO | Found in trans w/A467T and also in trans w/ Q308H | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| SCAE | Found in trans w/L304R in a 20 y.o. female w/ spinocerebellar ataxia epilepsy syndrome and mtDNA deletions | Not found in 300 healthy French control chromosomes | (Naimi et al., 2006) | PubMed | ||
| PEO, ataxia, and epilepsy | Found as a homozygous mutation in 13 pts. ranging in age from 2 to 19 yrs. One heterozygous 55 y.o. pt. with epilepsy. Also found in trans w/A467T in 7 pts. Ranging in age from 14 to 36 yrs. All w/ wide spectrum of mitochondrial disease. | Studied in 26 mitochondrial disease patients | (Tzoulis et al., 2006) | PubMed | ||
| Ataxia Neuropathy | A biochemical study of W748S pol gamma which exhibited low DNA polymerase activity, low processivity and a severe DNA-binding defect, and is commonly found in cis w/E1143G | (Chan et al., 2006) | PubMed | |||
| Alpers | Found in cis w/K561M and found in cis with E1143G. Both patients had mtDNA depletion | Sarzi, et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation W748S with E1143G. | (Sarzi, et al. 2007) | PubMed | ||
| Alpers, Ataxia Neuropathy, and arPEO+ | Found in trans w/ G848S, and in cis w/ Q479H-E1143G. Also found in trans w/ A467T. arPEO+ as a compound w/ E1143G | (Wong et al., 2008) | PubMed | |||
| Alpers | Homozygous, juvenile onset | (Uusimaa et al., 2008) | PubMed | |||
| Alpers | Found in trans w/ [R852C and G11D], and found in 2 additional pts. in trans w/T914P. Found homozygous in one pt. Found in trans w/ G848S. Found in trans w/[P587L and P589L]. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| PEO and Alpers | Found in trans w/ A467T. In a 2nd pt., found in cis w/ E1143G and in trans w/ G11D and R852C. | (Stewart et al., 2009) | PubMed | |||
| Alpers | In cis w/E1143G and in trans w/ G484S | (Taanman et al., 2008) | PubMed | |||
| mtDNA depletion | In cis w/E1143G and in trans w/ H1110Y and Q1236H | (Taanman et al., 2008) | PubMed | |||
| Alpers | In cis w/ Q497H and E1143G, and in trans w/ G848S | Found in one child w/ a normal brain MRI | (Brunetti-Pierri et al., 2008) | PubMed | ||
| Alpers | Found in 2 infants in trans w/ Y1210X | (Spinazzola et al., 2009) | PubMed | |||
| Alpers | Found in trans w/ L244P | (Spinazzola et al., 2009) | PubMed | |||
| Alpers | Found in trans w/ D930N | (Spinazzola et al., 2009) | PubMed | |||
| Parkinsonism | Homozygous mutation w/ PEO, ataxia, peripheral neuropathy, and hearing loss | (Remes et al., 2009) | PubMed | |||
| Leigh Syndrome | Found in trans with G11D and R852C | (Naess, et al., 2009) | PubMed | |||
| PEO | Found in trans with G737R, and in a 2nd pt. in cis with P587L and in trans with T251I. | (Tzoulis, et al., 2009) | PubMed | |||
| PEO, ptosis, polyneuropathy, ataxia, and dysartria | Found in trans w/A467T and in compound w/ E1143G | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Epilepsy, myoclonus, polyneuropathy, ataxia, and cognitive delay; a 2nd pt. with epilepsy and MELAS-like symptoms | Found in trans w/ A467T. | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Found with A467T in 4 middle aged patients, 2 of which are sisters | (Schulte et al., 2009) | PubMed | |||
| Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Homozygous in a 39 yr. old patient | (Schulte et al., 2009) | PubMed | |||
| Hepatocerebral - Alpers symptoms | Found w/P1073L. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility | (Kurt et al., 2010) | PubMed | |||
| SANDO | Found in trans w/ P1073L. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility | (Posada et al., 2010) | PubMed | |||
| PEO, mtDNA deletions and neurological phenotypes | Found in trans with A467T and in cis with E1143G. Sensory ataxia, dysarthria, and opthalmoplegia. | 1:135 carrier frequency in a Finnish population | (Komulainen et al., 2010) | PubMed | ||
| Alpers | Homozygous in 3 siblings with mtDNA deletions, hearing loss, diabetes, dementia, dysphagia, and limb myopathy. Also found in trans w/ R722H in two siblings w/ Ptosis, epilepsy, mental retardation | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Alpers | Found in cis with E1143G and in trans with R807C in a 1 y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Alpers | Found in cis with E1143G and Q497H, and in trans with A467T in a 6 y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Alpers | Found in cis with E1143G and in trans with G848S in a 11 mo. old with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Alpers | Found in cis with 1143G and in trans with T914P in a 2.5 y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Ataxia and cerebellar atrophy | Found as a homozygote in a 30 y.o. pt. with peripheral neuropathy, ataxia, and fatigability | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| SANDO and PEO | Found in trans w/ A467T in a 54 y.o. with PEO, ptosis, ataxia, neuropathy, and SANDO | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in a 16 y.o. with seizures, dystonia, choria, neuropathy, and ptosis | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in a 25 y.o. pt. that is homozygous for the W748S mutation and S28C as a heterozygote with PEO, ataxia, ptosis, and hearing loss | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ D892fsX39 in a 9 mo. old pt. w/ a deceased sibling | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Seizures | Found in trans w/ G848S in a 5 y.o. pt. w/myclonic seizures, liver failure, and hypotonia | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Alpers | Found in trans w/ Q449X in a 21 y.o. with seizures | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ G848S in a 7 y.o. w/ seizures and cortical blindness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ G848S in a 3 y.o. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Found in trans w/ G8484S in a 6 y.o. pt. with GI issues and irregular occipital lobe. Sibling died from VPA induced organ failure. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Seizures | Found in trans w/A467T in an 18 y.o. with ataxia, seizures, dystonia, and optic atrophy. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in trans w/ R953C in a 51 y.o. w/ peripheral neuropathy, ptosis, hypotonia, ataxia, and seizures. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ T914P in a 5 y.o. w/ seizures | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ T914P in an 8 mo. w/ seizures, hypotonia, abnormal MRI, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ A467T in a 29 y.o. symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Seizures and liver failure | Found in trans w/ M797del in a 1 y.o. with seizures and hepatic failure | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures and liver failure | Found in trans w/ G888D in a 2 y.o. w/ seizures, hepatic failure, ketosis and abnormal MRI | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Alpers | Found in trans w/ R852H in a 3 y.o. w/ Alpers | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| MSCAE | Found in trans w/ T914P in a 15 y.o. female with mitochondrial spinocerebellar ataxia and epilepsy. | (Hinnell et al., 2012) | PubMed | |||
| Alpers | Found in trans w/G848S in a 6 yr. 4 mo. with microvesicular fatty changes of the liver, myclonic seizures, and ataxia | (Hunter et al., 2011) | PubMed | |||
| Alpers | found in trans w/G8484S in a 6 yr. 9 mo. with seizures, developmentally delayed, and ataxia. | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found w/ E1143G and R232H in a pediatric patient w/mitochondrial encelphalomyopaty, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| Alpers | Found w/M1163R and E1143G in a pediatric patient w/mitochondrial encelphalomyopaty, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| MNGIE-like | Found in a 25 y.o. female as a homozygous mutation. Patient had migraines, ptosis, PEO, exercise intolerance, peripheral neuropathy, and ataxia. | (Tang et al., 2012) | PubMed | |||
| MNGIE-like | Found in compound with R953C in a 50y.o. male with cognitive impairment, muscle weakness, diarrhea, vomiting, ptosis, and opthalmoparesis. | (Tang et al., 2012) | PubMed | |||
| Alpers and PEO | Found in trans with R852C in a pediatric female patient with hypotonia, developmental delay, ataxia, and seizures | (Vasta et al., 2012) | PubMed | |||
| MIRAS | Mother and son were homozygous for E1143G in cis with E1143, and the unaffected father was heterozygous for W748S in cis with E1143G. Both mother and son had decreased mtDNA and spinocerebellar ataxias with presentation in late 30's and early 40's. | Frequencies in Europe for W748S+E1143G or A467T range from 0.6% in Belgium, 0.8% in Finland, and 2% in Finland | (Palin et al., 2012) | PubMed | ||
| Torticollis and PEO | Found in trans w/A467T in a 43 y.o. female with abnormal gait, ataxia, PEO, and head jerks. | (Tuladhar et al., 2012) | PubMed | |||
| Parieto-occipital lobe epilepsy | Found in trans w/ A467T in a 16 y.o. female with seizures, headaches, cerebellar ataxia, axonal neuropathy, visual impairment, and impaired cognitive function | (Roshal et al., 2011) | PubMed | |||
| PEO | Found in trans w/A467T in a 24 y.o. female with arPEO, cerebellar ataxia, and mtDNA deletions | (Lax et al., 2012b) | PubMed | |||
| PEO | Found in trans w/ R1096C in a 49 y.o. male with PEO, ptosis, epilepsy and peripheral neuropathy | (Lax et al., 2012a) | PubMed | |||
| PEO | Found in trans w/ A467T in a 47 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| PEO | Found in trans w/A467T in a 48 y.o. male with PEO, ptosis, ataxia and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| Epilepsy | Found in trans w/A467T in a 18 y.o.female male with epilepsy, ataxia and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| Epilepsy | Found in trans w/A467T in a 20 y.o. female male with epilepsy, ataxia and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| F749S | 2246 t→c (exon 13) | Alpers | Found in compound with A467T | Not found in 300 control chromosomes | (Nguyen et al., 2006) | PubMed |
| PEO | Found in trans w/ c.3104 +3a→t in a 66 y.o. w/ PEO, ptosis, myopathy, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in a 6 y.o. w/ seizures | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ A467T in an 8 mo. symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Optic atrophy | Found in trans w/c.3104+3A>T in a 65 y.o. male with ptosis, dysphagia, exercise induced myalgia, limb weakness, and diabetes. | (Milone et al., 2011) | PubMed | |||
| L752P | 2255 t→c (exon 13) | Epilepsy, seizures, VPA induced liver failure | Found in trans w/W748S and E1143G | (Zsurka, et al., 2008) | PubMed | |
| H754Q | 2262 c→g (exon 13) | Seizures and hepatic failure | Found in trans w/ A467T in 2 y.o. w/ seizures, hepatic failure, cerebellar atrophy, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| K755E | 2263 g→a (exon 13) | Hypoketotic, hypyoglycaemial, and liver dysfunction | Compound heterozygote w/ L623W | Not found in 200 healthy controls | (Bortot, et al., 2009) | PubMed |
| G763R | 2287 g→c (exon 14) | PEO, SANDO | ar, Found as a homozygous mutation in PEO-SANDO | Not found in 500 ethnically-matched control chromosomes | (Santoro et al., 2006) | PubMed |
| P765T | 2293 c→a (exon 14) | Ataxia neuropathy spectrum and gastroparesis | Found as a homozygous mutation in a 52 y.o. woman with ptosis, ataxia neuropathy, gastroparesis, and opthalmoplegia | (Bostan et al., 2012) | PubMed | |
| A767D | 2300 c→a (exon 14) | Alpers | Found as compound in trans with G737R | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| G785fs21X | 2354 ins g stop @ 806 (exon 14) | PEO | ar, Compound with T251I | Absent in 100 control DNA samples | (Lamantea et al., 2002) | PubMed |
| R790H | 2369 g→a (exon 14) | SNP | Reference # rs191490663 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusID=5428 | PubMed | |
| M797del | 2391-2393 gat de (exon 14) | Seizures and liver failure | Found in trans w/ W748S in a 1 y.o. with seizures and hepatic failure | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| A804T | 2410 g→a (exon 14) | Fatigue, muscle complaints, and bulbar dysarthria | ar, found in one 55 yr. old pt. | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed |
| R807H | 2420 g→a (exon 14) | Seizures and hepatic failure | Found in trans w/ A467T in a 1 y.o. with seizures, hepatic failure, hypotonia, and failure to thrive | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| R807P | 2420 g→c (exon 14) | PEO | Sporadic Compound with T251I | (Del Bo et al., 2003) | PubMed | |
| PEO | Found in compound w/T251I/ P587L in1 pt. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions. | Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians | (Di Fonzo et al., 2003) | PubMed | ||
| R807C | 2419 c→t (exon 14) | SANDO | Found in compound w/P648R in a 39 y.o. patient. | (Gago et al., 2006) | PubMed | |
| Alpers | Found in trans with E1143G and W748S in a 1 y.o. with epilepsy and Encephalopathy | (Isohanni et al., 2011) | PubMed | |||
| Ptosis and myopathy | Found as a heterozygous mutation in a 74 y.o. male with myopathy, ptosis, and diplopia | (Ferreira et al., 2011) | PubMed | |||
| SANDO | Found in trans with P648R in a 49 y.o. pt. with SANDO and mtDNA deletions. | (Ferreira et al., 2011) | PubMed | |||
| Liver failure | Found in trans w/ A467T in a 1 y.o. w/ encephalopathy, liver failure, and lactic acidosis | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| 4.7kb deletion of exons 15-21 | Intronic deletion starting in intron 14 (87,662,154) thru intron 21 (87,666,650), excising exons 15-21. | Alpers | Found as a compound heterozygote w/ A467T. Patient had early on set of Alpers and died at the age of 3.5 y.o.. The father carried the A467T mutation, and the mother the deletion. | (Compton et al., 2010) | PubMed | |
| Alpers | Found as a compound heterozygote w/ A467T in a 3.5 y.o. The father carried the A467T mutation, and the mother the deletion. | (Tang et al. 2011) | PubMed | |||
| Alpers | Found in trans w/A467T in a 2 y.o. w/seizures, developmentally delayed, and ataxia | (Hunter et al., 2011) | PubMed | |||
| c. 2480+1g>a | 2480+1 g→a splice site (exon 15) | Alpers | Found in trans w/ W748S-E1143G | (Wong et al., 2008) | PubMed | |
| IVS15-9- c.2485del 12bp | 2485 del 12bp (exon 16) | Alpers | Splice site mutation 3'exon15/intron junction, Found in trans with A467T | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| IVS16-10 c>t | IVS16-10 c>t (exon 16) | Cerebellar ataxia, sensory neuropathy, and dysphagia | Homozygous. Found in a 60 yr. old patient | (Schulte et al., 2009) | PubMed | |
| Y831F | 2492 a→t (exon 16) | Reference # rs41549716 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=41549716 | PubMed | ||
| Y831S | 2492 a→c (exon 16) | Reference # rs41549716 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=41549716 | PubMed | ||
| Y831C | 2492 a→g (exon 16) | Most likely a neutral polymorphism, but found in PEO and parkinsonism. | Ad in PEO and Parkinsonism. Found in high percentage in healthy controls in three studies. | (Barthelemy et al., 2002) | PubMed | |
| Most likely a neutral polymorphism, but found in PEO and parkinsonism. | Ad in PEO and Parkinsonism. Found in high percentage in healthy controls in three studies. | Mancuso 2004: Not seen in 120 control subjects | (Mancuso et al., 2004b) | PubMed | ||
| Most likely a neutral polymorphism, but found in PEO and parkinsonism. | Ad in PEO and Parkinsonism. Found in high percentage in healthy controls in three studies. | Stopinska 2006: present in the Polish population at a frequency of 2.25%. | (Stopinska et al., 2006) | PubMed | ||
| Most likely a neutral polymorphism, but found in PEO and parkinsonism. | Ad in PEO and Parkinsonism. Found in high percentage in healthy controls in three studies. | Tiangyou 2006: Found at the same frequency in age-matched controls. | (Tiangyou et al., 2006) | PubMed | ||
| Most likely a neutral polymorphism, but found in PEO and parkinsonism. | Ad in PEO and Parkinsonism. Found in high percentage in healthy controls in three studies. | Luoma 2007: Found in <1% of healthy controls | (Luoma et al., 2007) | PubMed | ||
| Heterozygous, hypotonia, Autism, neuropathy, ataxia, hearing loss, short stature, muscle weakness, fatigue | (Wong et al., 2008) | PubMed | ||||
| mtDNA depletion | In trans w/ H1134R | (Taanman et al., 2008) | PubMed | |||
| mtDNA deletions and seizures | Heterozygous mutation found in a 34 y.o. woman with seizures, opthalmoparesis, ptosis,, peripheral neuropathy….. | 2 in 322 mitochondrial disease patients | (Woodbridge et al., 2012) | PubMed | ||
| Muscle weakness | Heterozygous mutation found in a 46 y.o. woman with proximal weakness and myagia, and muscle twitches. | 2 in 322 mitochondrial disease patients | (Woodbridge et al., 2012) | PubMed | ||
| G848S | 2542 g→a (exon 16) | PEO | Compound with T251I | Lamantea, 2002: absent in 100 control DNA samples | (Lamantea et al., 2002) | PubMed |
| Alpers | Found in compound w/A467T in a 6 mo. male w/ | Ferrari et al., 2005 reported 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. | (Ferrari et al., 2005) | PubMed | ||
| Alpers | Found as compound W748S/E1143G. | (Davidzon et al., 2005) | PubMed | |||
| PEO | Compound with T251I and P587L in a 75 y.o. male | (Kollberg et al., 2005) | PubMed | |||
| Alpers | Found as compound in Alpers with A467T and also in trans w/ W748 /E1143G. | (Nguyen et al., 2005) | PubMed | |||
| Alpers | Found as compound in Alpers with A467T in a 6 mo. female | de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder | (de Vries et al., 2007) | PubMed | ||
| Alpers | Found as compound with A467T in a 6 mo. female w/ liver failure and encephalopathy | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| Liver failure, encephalopathy, and epilepsy | Found as compound with A467T in a 3 mo. male w/ liver failure and encephalopathy | Not found in 200 control alleles | (Kollberg et al., 2006) | PubMed | ||
| MELAS | Found w/ R627Q; heterozygous mutation; w/ mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. | (Deschauer et al., 2007) | PubMed | |||
| Alpers | Found in trans with A467T, Q497H, W748S, and E1143G. Also found in trans w/ T251I-P587L. | (Wong et al., 2008) | PubMed | |||
| Alpers | Found in trans w/W748S, and in a 2nd pt. in trans w/A467T. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| PEO and Ataxia | In trans w/ G746S and E1143G. Also found in trans w/ A467T. | Found in one child with a normal brain MRI. | (Stewart et al., 2009) | PubMed | ||
| Leigh Syndrome | In trans w/R232H | (Taanman et al., 2008) | PubMed | |||
| Alpers | In trans w/E1143G +W748S | (Taanman et al., 2008) | PubMed | |||
| Alpers | Found in trans w/ Q497H, W748S, and E1143G. | (Brunetti-Pierri et al., 2008) | PubMed | |||
| Myopathy and gastrointestinal obstruction | Found in trans w/ R227W with mtDNA depletion and Cox deficient muscle fibers | (Giordano et al., 2009) | PubMed | |||
| mtDNA depletion | Found in trans with A467T | (Roels, et al., 2009) | PubMed | |||
| Ptosis | ar, found in trans w/ T251I+P587L | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Found with R627Q in a 35 yr. old patient | (Schulte et al., 2009) | PubMed | |||
| Alpers | Found in trans with A467T | (Hasselmann et al., 2009) | PubMed | |||
| Hepatocerebral - Alpers symptoms | Found in trans w/P1073L. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility | (Kurt et al., 2010) | PubMed | |||
| SANDO | Found sporadically w/T251I and P587L in a 80 yr. old male | (Weiss and Saneto, 2010) | PubMed | |||
| Alpers | Found in trans with W748S and E1143G in a 11 mo. old with epilepsy and encephalopathy | (Isohanni et al., 2011) | PubMed | |||
| Liver Diseases | Found in trans w/A467T in a 2 y.o. pt. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in an 8 y.o. pt. with seizures, muscle weakness, hypotonia, ataxia, hearing loss, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in a 1 y.o. with seizures, elevated transaminases, and increased signal basal ganglia | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ W748S in a 5 y.o. pt. w/myclonic seizures, liver failure, and hypotonia | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ W748S in a 7 y.o. w/ seizures and cortical blindness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ W748S in a 3 y.o. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Found in trans w/ W748S in a 6 y.o. pt. with GI issues and irregular occipital lobe. Sibling died from VPA induced organ failure. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Seizures | Found as a homozygote in a 5 y.o. with seizures, an abnormal MRI, and abnormal respiratory enzymes. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Encephalopathy | Found in trans w/ R1096C in a 2 y.o. w/ hypotonia, ptosis, hepatic failure, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Failure to thrive | Found in trans w/ P1073L in a 2 y.o. w/ hypotonia, and gastro-esophageal reflux. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in trans w/ T25IL and P587L in an 80 y.o. w/ ptosis, PEO, peripheral neuropathy, and abnormal muscle histology. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A143V in a 4 y.o. w/ hypotonia, encephalopathy, seizures, hepatic failure, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A143V in a 38 y.o. w/ ataxia, peripheral neuropathy, hearing loss, and seizures | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found in trans w/ c.3104+3a→t in a 63 y.o. w/ PEO, ptosis, hearing loss, muscle weakness and ragged red fibers | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A143V in an 8 y.o. w/ seizures and an abnormal MRI | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Found in trans w/ A143V in a 37 y.o. symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Alpers | Found in trans w/W748S in a 6 yr. 4 mo. with micro-vesicular fatty changes of the liver, myclonic seizures, and ataxia | (Hunter et al., 2011) | PubMed | |||
| Alpers | found in trans w/W7484S in a 6 yr. 9 mo. with seizures, developmentally delayed, and ataxia. | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/A467T in a 3 y.o. w/seizures, developmentally delayed, and ataxia | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/A467T in a 11 mo. old w/seizures and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/ A467T in a pediatric patient w/mitochondrial encelphalomyopaty, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| Alpers | Found in trans w/A467T in a 10 mo. old female with seizures and brain stem dysfunction. History revealed that a 24 y.o. cousin died from Alpers whom harbored a homozygous A467T variant. | (McCoy et al., 2011) | PubMed | |||
| Alpers and Leigh's encephalopathy | Found in trans w/A467T in a 3.5 mo. old female with seizures and Alpers. Post mortem studies revealed Leigh's encephalopathy | (Scalais et al., 2012) | PubMed | |||
| Optic atrophy | Also found in w/ c.3104+3A>T in a 63 y.o. male with exercise intolerance, hearing loss, ptosis, and parkinsonism. | (Milone et al., 2011) | PubMed | |||
| Parkinsonism | Found in trans w/S1104C in a 59 y.o. male with mtDNA deletions and cerebellar ataxia | (Lax et al., 2012b) | PubMed | |||
| PEO | Found in trans w/G746S in a 36 y.o. male with PEO, peripheral neuropathy, and ataxia | (Lax et al., 2012a) | PubMed | |||
| T849H | 2544 (insertion of c with fs868X) (exon 16) | Alpers | Found in trans with A467T and in cis with Q1236H | (Wong et al., 2008) | PubMed | |
| T851A | 2551 a→g (exon 16) | Alpers | Found in trans w/R1047W. | Not found in over 100 control alleles | (Wiltshire et al., 2008) | PubMed |
| Alpers | Found in trans w/H277L. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Opthmalplegia and seizures | Found in trans w/P163S in a 21 y.o. female with peripheral neuropathy, seizures, dysarthria and bilateral ptosis | 2 in 322 mitochondrial disease patients | (Woodbridge et al., 2012) | PubMed | ||
| Opthmalplegia and peripheral neuropathy | Found in trans w/N468D in a 49 y.o. female with ptosis, lower limb weakness, sensory ataxia, gastrointestinal symptoms, and peripheral neuropathy | 2 in 322 mitochondrial disease patients | (Woodbridge et al., 2012) | PubMed | ||
| R852C | 2554 c→t (exon 16) | Alpers | Compound with A467T | Not found in 300 control chromosomes | (Nguyen et al., 2006) | PubMed |
| Ataxia Neuropathy | Found in trans w/ G11D-R627Q | (Wong et al., 2008) | PubMed | |||
| Alpers | Found in cis w/G11D and in trans w/W748S, and in a 2nd pt. found in cis w/G11D and in trans w/A467T. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Alpers | Found in cis w/G11D and in trans w/ A467T. In a 2nd pt., found in cis w/G11D and in trans w/ W748S and E1143G. | (Stewart et al., 2009) | PubMed | |||
| Leigh Syndrome | Found in cis with G11D and in trans with W748S | (Naess, et al., 2009) | PubMed | |||
| Multiple system atrophy | Found with G11D in a 58 y.o. female with progressive cerebellar atrophy. Pt. had mtDNA deletions and mtDNA depletion. | (Mehta et al., 2011) | PubMed | |||
| Seizures and liver failure | Found in trans w/ A467T and in cis w/ G11D in a 8 mo. w/ seizures, liver failure, and lactic acidosis. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Encephalopathy | Found in cis w/ G11D and in trans w/ R627Q in a 25 y.o. w/ dementia, encephalopathy, and stroke. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Alpers | Found in trans w/A467T in a 5 y.o. w/seizures, ataxia, and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/A467T in a 21 mo. old female with blindness, anarthria, hypotonia, and epilepsy | (McCoy et al., 2011) | PubMed | |||
| Alpers and PEO | Found in trans with W748S in a pediatric female patient with hypotonia, developmental delay, ataxia, and seizures | (Vasta et al., 2012) | PubMed | |||
| R852H | 2555 g→a (exon 16) | Alpers | Found in trans w/ W748S in a 3 y.o. w/ Alpers | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| R853W | 2557 c→t (exon 16) | PEO with ptosis | Found as compound in trans with P587L Parkinsonism in compound in trans with G737R | 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. | (Gonzalez - Vioque et al., 2006) | PubMed |
| Parkinsonism | (Davidzon et al., 2006) | PubMed | ||||
| R853Q | 2558 g→a (exon 16) | Myocerebrohepatopathy | In trans with T251I-P587L | (Wong et al., 2008) | PubMed | |
| V855L | 2563 g→t (exon 16) | Seizures | Found in trans w/ G737R in an 8 mo. w/ seizures, liver failure, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| V855A | 2564 t→c (exon 16) | Heterozygous with muscle weakness. | (Wong et al., 2008) | PubMed | ||
| A862T | 2584 g→a (exon 16) | Ataxia Neuropathy | Compound heterozygous with R964C | (Wong et al., 2008) | PubMed | |
| PEO with ataxia | In trans w/R1047W | (Stewart et al., 2009) | PubMed | |||
| Cerebellar ataxia, neuropathy, epilepsy, and restless leg syndrome | Found heterozygous with R964C in 2 siblings that died in their early 20's | (Stricker et al., 2009) | PubMed | |||
| Alpers-like | Found in trans with R1081Q in a 7 y.o. male with Alpers-like symptoms. Affected sibling. | (Ferreira et al., 2011) | PubMed | |||
| Alpers-like | Found in trans with R1081Q in a 4 y.o. male with Alpers-like symptoms. Affected sibling. | (Ferreira et al., 2011) | PubMed | |||
| Myelopathy,myopathy, peripheral neuropathy and subcortical grey matter degeneration | Found in trans w/H277L in a 66 y.o. female with mtDNA deletions and subcortical grey matter degeneration | (McKelvie et al., 2012) | PubMed | |||
| PEO | Found in trans w/ R1047W in a 61 y.o. female with PEO, ptosis, peripheral neuropathy, ataxia, and dysarthria. | (Lax et al., 2012a) | PubMed | |||
| N864S | 2591 a→g (exon 16) | PEO | Found as compound with T251I-P587L | Not found in 280 control chromosomes | (Van Goethem et al., 2003c) | PubMed |
| IVS16-10 c>t | IVS16-10 c>t (exon 16) | Cerebellar ataxia, sensory neuropathy, and dysphagia | Homozygous. Found in a 60 yr. old patient | (Schulte et al., 2009) | PubMed | |
| R869Q | 2606 g→a (exon 17) | Myopathy w/ neurogenic atrophy; sensomotor axonal polyneuropathy, ataxia, and ptosis | Autosomal recessive, found in a 32 yr. old pt. | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed |
| PEO | Found in trans w/ K319E in a 44 y.o. w/ PEO, ataxia, neuropathy, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| E873X | 2617 g→t (exon 17) | Alpers | Found in trans with A467T and under goes nonsense-mediated decay for mono-allelic expression of POLG | Not found in 40 alleles from non-Alpers mitochondrial disease patients | (Chan et al., 2005b) | PubMed |
| Alpers | Found in trans with A467T | Not found in 40 alleles from non-Alpers mitochondrial disease patients | (Naviaux and Nguyen, 2004) | PubMed | ||
| Alpers | Found in trans w/A467 in and 18 mo. old male w/ mtDNA depletion | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Q879H | 2637 g→t (exon 17) | Liver failure and encephalopathy | Found in cis with E1143G and in trans with A467T-T885S | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| Alpers w/ valproate-induced hepatic failure | Found in cis with E1143G and in trans with A467T-T885S in a 2 y.o. male | (McFarland et al., 2009) | PubMed | |||
| T885S | 2653 a→t (exon 17) | Alpers | Found in cis with A467T and in trans with Q879H-E1143G | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| Alpers w/ valproate-induced hepatic failure | Found in cis with A467T, and in trans w/Q879H and E1143G | (McFarland et al., 2008) | PubMed | |||
| L886P | 2657 t→c (exon 17) | Alpers | Found in trans w/ A467T | (Wong et al., 2008) | PubMed | |
| G888S | 2662 g→a (exon 17) | Alpers | Compound heterozygous with L83P in 10 yr. old | (Bao et al., 2007) (Wong et al., 2008) | PubMed | |
| G888D | 2663 g→a (exon 17) | Seizures and liver failure | Found in trans w/ W748S in a 2 y.o. w/ seizures, hepatic failure, ketosis and abnormal MRI | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| Alpers | Found in trans w/L304R in a patient showing psychomotor retardation, epileptic encephalopathy, progressive cerebral atrophy, and altered liver enzymes. | 1 of 52 pediatric patients suspected to have mitochondrial DNA depletion syndrome | (Navarro-Sastre et al., 2012) | PubMed | ||
| A889T | 2665 g→a (exon 17) | PEO | Sporadic / unknown Compound with R579W Compound with E1143G | Filosto, 2003: not detected in 120 healthy control alleles | (Filosto et al., 2003) | PubMed |
| PEO | Sporadic / unknown Compound with R579W Compound with E1143G | (Hisama et al., 2005) | PubMed | |||
| D892GfsX39 | 2675 ins g (exon 17) | Found in trans w/ W748S in a 9 mo. old pt. with a deceased sibling. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |
| E895G | 2684 a→g (exon 17) | Myopathic MDS | Found in one newborn with floppiness and 20% liver mtDNA depletion, heterozygous | (Spinazzola et al., 2009) | PubMed | |
| T914A | 2740 a→g (exon 18) | Multiple Sclerosis-like illness | Found as a heterozygous mutation w/Y452C in a 56 yr. old. Pt. first diagnosed w/ optic neuritis and MS 19 yrs. earlier. Currently has ragged-red muscle fibers, ptosis, myopathies, and mtDNA deletions. | (Echaniz-Laguana et al., 2010) | PubMed | |
| Alpers | Found in trans with A467T in a 9 mo. old with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| T914P | 2740 a→c (exon 18) | Alpers | Found in trans with A467T. | Not found in 300 control chromosomes | (Nguyen et al., 2006) | PubMed |
| Encephalopathy | Found in trans with A467T in an 8 y.o. male w/encephalopathy and myoclonus . | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| Alpers | Found in trans with A467T in a 7 mo. female w/ Alpers | Not found in 300 healthy French control chromosomes | (Naimi et al., 2006) | PubMed | ||
| Alpers | Found in trans w/ A467T | (Wong et al., 2008) | PubMed | |||
| adPEO | Heterozygous, Ptosis, exercise intolerance, fatigue, ragged red fibers | (Wong et al., 2008) | PubMed | |||
| Alpers | Found in trans w/R1096C, and in a 2nd pt. found in trans w/R627W. Also found in trans w/A467T in 2 other pts. Found in 2 additional pts. in trans w/W748S. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Alpers | In trans w/ A467T | (Taanman et al., 2008) | PubMed | |||
| Epilepsy, myoclonic, and developmental delay | ar, Found as a compound heterozygous mutation w/ A467T | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Epilepsy | Found heterozygous with A467T in a 10 mo. old male with myoclonic seizures and jerks, and developmental regression. | (Dhamija et al., 2011) | PubMed | |||
| Alpers | Found in trans with E1143G and W748S in a 2.5 y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in a 3 y.o. w/ seizures, hypotonia, encephalopathy, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ W748S in a 5 y.o. w/ seizures | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in a 5 y.o. w/ seizures, hearing loss, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ W748S in an 8 mo. w/ seizures, hypotonia, abnormal MRI, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in a 9 mo. w/ seizures, hypotonia, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures and liver failure | Found in trans w/ A467T in a 4 y.o. with liver failure, seizures, and failure to thrive | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found in trans w/ A467T in an 8 mo. w/ seizures, respiratory failure, and an abnormal MRI | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| MSCAE | Found in trans w/ W748S in a 15 y.o. female with mitochondrial spinocerebellar ataxia and epilepsy. | (Hinnell et al., 2012) | PubMed | |||
| W918R | 2752 t→c(exon 18) | PEO with Parkinsonism | ar, Compound (in trans) heterozygous with M430L | Absent in 200 control alleles | (Invernizzi et al., 2008) | PubMed |
| PEO | Found in trans with M430L in a 42 y.o. male with PEO and mtDNA | (Ferreira et al., 2011) | PubMed | |||
| G923D | 2768 g→a (exon 18) | PEO | Found as a homozygous mutation in 2 patients w/ mtDNA deletions. Also found as a heterozygous mutation with little or no symptoms. | Lamantea, 2002: absent in 100 control DNA samples | (Lamantea et al., 2002) | PubMed |
| PEO | ad PEO. Studied the pathological and biochemical consequences of several PEO mutations by modeling the amino acid changes and structure pol γ. In order to correlate mutation and disease severity. | (Graziewicz et al., 2004) | PubMed | |||
| PEO | Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci. | (Stuart et al., 2006) | PubMed | |||
| G923R | 2767 c→g (exon 18) | Reference # rs60636456 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=60636456 | PubMed | ||
| K925R fs42X | 2772_2773 delG | Prematurity, epilepsy, deafness, retinitis pigmentosa, hemiparesis, and liver failure | Found in trans w/A467T. | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed |
| D930N | 2788 g→a (exon 18) | Alpers | Infantile Alpers w/ bilateral lesions of thalami. Hepatocerebral MDS patient, Found in trans w/ W748S. | (Spinazzola et al., 2009) | PubMed | |
| H932Y | 2794 c→t (exon 18) | PEO and mtDNA deletions | Found in compound w/T251I/ P587L in1 pt. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions. | Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians | (Di Fonzo et al., 2003) | PubMed |
| PEO | Found in compound with G1051R in 2 family members PEO | not seen in 120 control subjects. | (Mancuso et al., 2004a) | PubMed | ||
| Isolated distal myopathy of the upper limbs w/ mtDNA depletion | (Giordano et al., 2010) | PubMed | ||||
| PEO | Found in trans w/ P587L and T251I in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Peripheral Neuropathy | Found in trans w/ T251I and P587L in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| S933R | 2799 t→g (exon 18) | PEO | Found in trans w/ Q1214LX in a 60 y.o. w/ PEO, dementia, myopathy, and abnormal muscle histology | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| Seizures | Found in trans w/ A957V in a 3 mo. w/ seizures, hypotonia, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| R943C | 2827 c→t (exon 18) | Myocerebrohepatopathy | In cis w/ E1143G and in trans w/G737R | (Wong et al., 2008) | PubMed | |
| PEO | Ad, and premature ovarian failure | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| R943H | 2828 g→a (exon 18) | PEO | ad PEO. Found in 2 siblings as a homozygous mutation | Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians | (Lamantea et al., 2002) | PubMed |
| PEO | ad PEO. Studied the pathological and biochemical consequences of several PEO mutations by modeling the amino acid changes and structure pol γ. In order to correlate mutation and disease severity. | (Graziewicz et al., 2004) | PubMed | |||
| PEO | Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci. | (Stuart et al., 2006) | PubMed | |||
| Premature ovarian failure | Ad, and premature ovarian failure | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| K947R | 2840 g→a (exon 18) | PEO and ovarian failure | Compound heterozygote found w/ expansion of a polyQ (18Q) stretch. | (Baruffini et al., 2011) | PubMed | |
| Y951N | 2851 t→a (exon 18) | Peripheral Neuropathy | Found as a heterozygous mutation in 22 y.o. w/ peripheral neuropathy | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| 3-methyl glutaconic aciduria | Found as a heterozygous mutation in a 23 y.o. female with progressive muscle weakness, cataracts, and ovarian dysgenesis | (Bekheirnia et al., 2012) | PubMed | |||
| R953C | 2857 c→t (exon 18) | PEO | ad | Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes. | (Luoma et al., 2004) | PubMed |
| Reference # rs11546842 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=11546842 | PubMed | ||||
| PEO | Found in trans w/ W748S in a 51 y.o. w/ peripheral neuropathy, ptosis, hypotonia, ataxia, and seizures. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Autosomal recessive PEO, found as a homozygous mutation in 3 affected siblings and heterozygous in 2 asymptomatic siblings from the same family. One unaffected sibling had no POLG mutations. Symptoms started in early 20's of the 3 affected siblings which include abnormal gait, parkinsonism, sensory neuropathy, cardiomyopathy, and depression. | (Gurgel-Giannetti et al., 2012) | PubMed | |||
| MNGIE-like | Found in compound with W748S in a 50y.o. male with cognitive impairment, muscle weakness, diarrhea, vomiting, ptosis, and opthalmoparesis. | (Tang et al., 2012) | PubMed | |||
| Y955C | 2864 a→g (exon 18) | PEO | ad PEO in a family w/ mtDNA deletions | absent in 432 control chromosomes | (Van Goethem et al., 2001) | PubMed |
| PEO | Found as a heterozygous mutation in 3 Belgian families w/ PEO | Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians | (Lamantea et al., 2002) | PubMed | ||
| PEO | ad PEO. Studied the pathological and biochemical consequences of several PEO mutations by modeling the amino acid changes and structure pol γ. In order to correlate mutation and disease severity. | (Graziewicz et al., 2004) | PubMed | |||
| Parkinsonism Premature ovarian failure Alzheimer's disease | Most severe autosomal dominant mutation in POLG, drastically lowers polymerase catalysis, promotes stalling and errors in replication. | Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes. | ( Luoma et al., 2004) | PubMed | ||
| PEO and Premature ovarian failure | Found as a heterozygous and homozygous mutation in 3 generations of women in the same family with Premature ovarian failure and PEO. Also found in trans w/Q1236H. | (Pagnamenta et al., 2006) | PubMed | |||
| PEO | Studied recombinant protein and found that the Y955C POLG enzyme cause error-prone DNA synthesis | (Ponamarev et al., 2002) | PubMed | |||
| PEO | Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci. | (Stuart et al., 2006) | PubMed | |||
| PEO | Studied the yeast homologue that had mtDNA depletion and deletions with altered dNTP pools | (Baruffini et al., 2006) | PubMed | |||
| PEO | Studied 4 pts. with adPEO and that were heterozygous for Y955C which revealed a low instance of mtDNA point mutations. | (Kollberg et al., 2005) | PubMed | |||
| PEO | Y955C POLG was targeted transgenically to the murine heart. The mice had cardiomyopathy and mtDNA depletion. | (Lewis et al., 2007) | PubMed | |||
| PEO/Alzheimer's | Myopathy, COX deficient muscle fibers, and mtDNA depletion found in 2 siblings who developed Alzheimer's and thought to have aged prematurely. | (Melberg et al., 2005) | PubMed | |||
| Found as a heterozygous mutation w/ hearing loss, failure to thrive, generalized ETC complex deficiency | (Wong et al., 2008) | PubMed | ||||
| PEO | Found in cis w/ G517V in a 47 y.o. w/ PEO, ptosis, myopathy, and neuropathy | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| PEO | Found as a heterozygous mutation in a 45 y.o. w/ myopathy and PEO | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| A957S | 2869 g→t (exon 18) | PEO | Found as both a heterozygous and as a homozygous mutation in one individual in two Sicilian families. | Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians | (Lamantea et al., 2002) | PubMed |
| PEO | ad PEO. Studied the pathological and biochemical consequences of several PEO mutations by modeling the amino acid changes and structure pol γ. In order to correlate mutation and disease severity. | (Graziewicz et al., 2004) | PubMed | |||
| PEO | Demonstrate that S. cerevisiae provides a useful in vivo system for quickly evaluating the biological consequences of identified, or suspected, PEO mutation loci. | (Stuart et al., 2006) | PubMed | |||
| A957P | 2869 g→c (exon 18) | Alpers | Found in compound w/A467T in a 8 mo. old male w/ multiple complex deficiencies | de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder | (de Vries et al., 2007) | PubMed |
| Alpers | Found in compound w/A467T in a 6 mo. old w/ infantile hepatocereberal syndrome. | Ferrari, 2005: absent in 200 consecutive control individuals from Northern continental Europe as well as 350 Italian controls | (Ferrari et al., 2005) | PubMed | ||
| Epilepsy, liver failure, occipital strokes, and growth retardation | ar, found as a compound heterozygous mutation w/ A467T | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| A957V | 2870 c→t (exon 18) | Seizures | Found in trans w/ C1077G in a 2 y.o. w/ seizures, encephalopathy, and hypotonia | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| Found in trans w/ G737R in a 4 mo. Symptoms not noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | |||
| Seizures | Found in trans w/ S933R in a 3 mo. w/ seizures, hypotonia, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| F961S | 2882 t → c (exon 18) | PEO | ad PEO | (Adachi et al., 2002) | PubMed | |
| A962T | 2884 g→a (exon 18) | Ataxia | Found in trans w/ R964C in a 14 y.o. w/ ataxia, muscle weakness, and central hypoventilation | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| R964C | 2890 c → t (exon 18) | Mitochondrial toxicity susceptibility to NRTIs | Found in a HIV1 patient with hyperlactatemia following 1 yr. of d4T and 3TC anti-viral treatment | Not found in 26 Thai HIV-1-infected individuals, or 110 healthy volunteers | (Yamanaka et al., 2007) | PubMed |
| Ataxia Neuropathy | Found in trans w/ A862T, and found as a heterozygous mutation w/ ataxia and hypotonia | (Wong et al., 2008) | PubMed | |||
| Cerebellar ataxia, neuropathy, epilepsy, and restless leg syndrome | Found heterozygous with A862T in 2 siblings that died in their early 20’s | (Stricker et al., 2009) | PubMed | |||
| Ataxia | Found in trans w/ A962T in a 14 y.o. w/ ataxia, muscle weakness, and central hypoventilation | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| L965X | 2894 t→g (exon 18) | PEO | ar, found in cis with E1143G and in trans with R627Q-Q1236H | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| L966R | 2897 t→g (exon 18) | Alpers | Compound with A467T | Not found in 300 control chromosomes | (Nguyen et al., 2006) | PubMed |
| Alpers | In trans w/A467T. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Alpers | Found in trans w/A467T in a 1 y.o. w/ seizures and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/A467T in a 1 y.o. w/ seizures and developmentally delayed | (Hunter et al., 2011) | PubMed | |||
| Alpers | Found in trans w/A467T in a 17 mo. old male with seizures and encephalopathy | (McCoy et al., 2011) | PubMed | |||
| S998W | 2993 c→g (exon 19) | Reference # rs79840247 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=79840247 | PubMed | ||
| S998L | 2993 c→t (exon 19) | PEO | Found as a compound heterozygote with D1184H in a 64 y.o. female with PEO, bilateral ptosis, and encephalopathy. | (Martikainen et al.,) | PubMed | |
| W1020X | 3057 g→a (exon 19) | Alpers | Compound with A467T | (Nguyen et al., 2005) | PubMed | |
| Q1024X | 3067 c→t (exon 20) | Seizures | Found in trans w/ A467T in a 2 y.o. w/seizures, hearing loss, and hemiparesis | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| c. 3104 +3a→t | 3104 +3a→t (splice variant between ex. 19 and 20) | PEO | Found in trans w/ F749S in a 66 y.o. w/ PEO, ptosis, myopathy, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| Optic atrophy | Found in trans w/F749S in a 65 y.o. male with ptosis, dysphagia, exercise induced myalgia, limb weakness, and diabetes. Also found in trans w/ G8484S in a63 y.o. male with exercise intolerance, hearing loss, ptosis, and parkinsonism. | (Milone et al., 2011) | PubMed | |||
| PEO | Found in trans w/ G848S in a 63 y.o. w/ PEO, ptosis, hearing loss, muscle weakness and ragged red fibers | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| V1044A | 3131 t→c (exon 20) | Alpers | Found in trans with R722H in a 2.5 y.o. old with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed |
| R1047Q | 3140 g→a (exon 20) | PEO | Sporadic / unknown | Not found in 250 control individuals | (Agostino et al., 2003) | PubMed |
| R1047W | 3139 c→t (exon 20) | Alpers | Compound in trans with T851A | Not found in over 200 control alleles | (Wiltshire et al., 2008) | PubMed |
| PEO | ar, in trans w/ A862T | (Stewart et al., 2009) | PubMed | |||
| PEO | Found in trans w/ A862T in a 61 y.o. female with PEO, ptosis, peripheral neuropathy, ataxia, and dysarthria. | (Lax et al., 2012a) | PubMed | |||
| K1050RfsX44 | 3149 del a (exon 20) | Seizures | Found in trans w/ A467T in a 4 y.o. w/ seizures, ataxia, hypotonia, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| G1051R | 3151 g→c (exon 20) | PEO, SANDO | ar Found as compound with H932Y | not seen in 120 control subjects. | (Mancuso et al., 2004a) | PubMed |
| P1073L | 3218 c→t (exon 20) | Hepatocerebral - Alpers symptoms | Found in trans w/A467T in 2 pt., in trans w/ W748S in 1 pt., and in trans with G848S in 1 pt. Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility. | (Kurt et al., 2010) | PubMed | |
| Alpers | Found as a compound heterozygote w/ S305R in a 9 mo. pt. w/ Alpers | (Baruffini et al., 2011) | PubMed | |||
| Failure to thrive | Found in trans w/ G848S in a 2 y.o. w/ hypotonia, and gastro-esophageal reflux. | (Tang et al., 2011) | PubMed | |||
| G1076V | 3227 g→t (exon 20) | PEO | Sporadic / unknown | Not detected in 120 healthy control alleles | (Filosto et al., 2003) | PubMed |
| C1077G | 3229 t →g (exon 20) | Seizures | Found in trans w/ A957V in a 2 y.o. w/ seizures, encephalopathy, and hypotonia | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| I1079L | 3235 a→c (exon 20) | adPEO | Heterozygous Hearing loss, and ptosis | (Wong et al., 2008) | PubMed | |
| R1081dup | 3240– 3242 ins ccg (R) (exon 20) | Alpers | Found in cis w/ L392V and in trans w/L304R | (Cardenas et al., 2010) | PubMed | |
| Seizures | Found in trans w/ L304R in a 1 y.o. w/ seizures and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| R1081Q | 3241 c→g (exon 20) | Alpers-like | Found in trans with A862T in a 7 y.o. male with Alpers-like symptoms. | (Ferreira et al., 2011) | PubMed | |
| Alpers-like | Found in trans with A862T in a 4 y.o. male with Alpers-like symptoms. Affected sibling | (Ferreira et al., 2011) | PubMed | |||
| Cerebellar ataxia | Found as a heterozygote in a 29 y.o. female with cerebellar ataxia and diabetes | (Ferreira et al., 2011) | PubMed | |||
| R1081P | 3242 g→c (exon 21) | PEO | Found in trans w/ L304R in a 10 y.o. w/ ataxia, seizures, PEO, and dystonia | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| F1092L | 3276 t→g (exon 21) | Reference # rs74034411 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=74034411 | PubMed | ||
| S1095R | 3285 c→g (exon 21) | adPEO | Hearing loss, ptosis, Muscle weakness, optic atrophy | (Wong et al., 2008) | PubMed | |
| 3286 c→g (exon 21) | Failure to thrive | ar, found in trans w/ D1184N. Aslo, impaired liver functions, deafness, and demyelating sensomotor neuropathy | <0.5% of Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | |
| Hepatic failure | Found in trans w/ A467T in a 6 mo. w/ hypotonia, liver failure, abnormal muscle histology, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| R1096C | 3286 c→t (exon 21) | PEO | Sporadic or ar in PEO | Agostino 2003: Not found in 250 individuals | (Agostino et al., 2003) | PubMed |
| Alpers | Found in trans with P648R in PEO-myopathy. Found as homozygous mutation with Q1236H in Alpers | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| Alpers | Found as compound w/ Q1236H . | (Wong et al., 2008) | PubMed | |||
| Alpers | Found in trans w/T914P, and homozygous in a 2nd pt. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) | PubMed | |||
| Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Found with R627Q in a 43 yr. old patient | (Schulte et al., 2009) | PubMed | |||
| Seizures | Found as a homozygote in an 8 mo. old pt. with encephalopathy and seizures. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found as a homozygote in a 1 y.o. with seizures and liver failure. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Encephalopathy | Found in trans w/ G848S in a 2 y.o. w/ hypotonia, ptosis, hepatic failure, and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| Seizures | Found as a homozygote in a 2 y.o. w/ seizures, lactic acidosis and developmentally delayed. | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| SANDO | Found in trans w/L591F in a 48 y.o. female with SANDO and dysphagia. | (Kurt et al. 2012) | PubMed | |||
| PEO | Found in trans w/ W748S in a 49 y.o. male with PEO, ptosis, epilepsy and peripheral neuropathy | (Lax et al., 2012a) | PubMed | |||
| PEO | Found in trans w/A467T in a 42 y.o. male with PEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| R1096H | 3287 g→a (exon 21) | Alpers | Found as a compound in trans with R627Q | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| S1104C | 3311 c→g (exon 21) | PEO | Sporadic / unknown Found as compound with A467T | Not found in 250 individuals | (Agostino et al., 2003) | PubMed |
| Parkinsonism | Found in trans w/G848S in a 59 y.o. male with mtDNA deletions and cerebellar ataxia | (Lax et al., 2012b) | PubMed | |||
| A1105T | 3313 g→a (exon 21) | PEO | Found as a heterozygous mutation and as a compound heterozygous mutation w/ N468D in 3 patients of the same family all w/PEO | Luoma, 2004: None noted in screening of 1640 healthy Finnish control chromosomes. | (Luoma et al., 2004) | PubMed |
| PEO | Found d as a compound heterozygous mutation w/ N468D in 3 patients w/ mtDNA deletions and mutations. Proposed replication stalling as the principal cause of deletion formation. | (Wanrooij et al., 2004) | PubMed | |||
| V1106I | 3316 g→a (exon 21) | PEO | ar, found in trans with T251I-P587L | Not found in 500 Italian controls. | (Horvath et al., 2006) | PubMed |
| H1110Y | 3328 c→t (exon 21) | infantile hepatocerebral mtDNA depletion | Heterozygous, found in cis Q1236H, & in trans w/ W748S+ E1143G | (Taanman et al., 2008) | PubMed | |
| L1113P | 3338 t→c (exon 21) | Seizures | Found in trans w/ A467T in a 1 y.o. with encephalopathy, seizures, and hepatic failure | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| R1128H | 3383g→a (exon 21) | Microcephaly | Heterozygous, found w/ G517V | (Wong et al., 2008) | PubMed | |
| H1134R | 3401 a→g (exon 21) | infantile hepatocerebral mtDNA depletion | Heterozygous, found in trans with Y831C | (Taanman et al., 2008) | PubMed | |
| E1136K | 3406 g→a (exon 21) | infantile hepatocerebral mtDNA depletion | Heterozygous, found T251I+P587L | (Taanman et al., 2008) | PubMed | |
| Reference # 56047213 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=56047213 | PubMed | ||||
| R1138C | 3412 c→t (exon 21) | PEO | Found in trans w/ A467T | (Wong et al., 2008) | PubMed | |
| R1142W | 3424 c→t (exon 21) | Neutral polymorphism | 0.6% of 450 individuals | (GeneSNPs, 2004) | PubMed | |
| Reference # rs2307442 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307442 | PubMed | ||||
| E1143G | 3428 a→g (exon 21) | Neutral polymorphism | Neutral polymorphism but may modulate disease mutations | SNP at 3.7% of 450 individuals of European descent. Not found in Asian or African populations | (GeneSNPs, 2004) | PubMed |
| PEO | Found as a heterozygous mutation | Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians | (Di Fonzo et al., 2003) | PubMed | ||
| Ataxia | Found as a homozygous and heterozygous mutation, or in compound w/ W748S all within the same family | (Van Goethem et al., 2004) | PubMed | |||
| Neutral polymorphism but may modulate disease mutations | Found in cis w/ A889T | (Hisama et al., 2005) | PubMed | |||
| Ataxia | Found as a homozygous mutation w/ W748S | Carrier frequency in the general Finnish population of 1:125 from 500 control chromosomes | (Hakonen et al., 2005) | PubMed | ||
| Alpers | Found in trans w/G848S and in cis w/E1143G in 4 children w/ hepatocerebral disorders and mtDNA depletion | Present in 3-5% of the control population | (Davidzon et al., 2005) | PubMed | ||
| Alpers | Found in ataxia-neuropathy in cis with W748S and in compound with G848S or A467T. | (Nguyen et al., 2005) | PubMed | |||
| Ataxia | Found in compound w/ Q497H and W748S | frequency of 0.03 | (Winterthun et al., 2005) | PubMed | ||
| Ataxia-neuropathy spectrum disorders | Studied the biochemical effects of E1143G in cis with other pathogenic mutations, and how it can modulate the effects of these mutations | (Chan et al., 2006) | PubMed | |||
| Liver failure, Neuropathy, and PEO | Found in trans w/ A467T/T885S and in cis w/ Q789H in an 2.5 y.o. old male with liver failure. Also found in trans w/A467T in a 15 y.o. male w/ PEO. Found in trans w/ S433C in a 25 y.o. male w/PEO. Found in cis w/ L965X and in trans w/ R627Q/Q1236H in a PEO patient. Found in trans w/G 517V in a 4 y.o. female and her father both w/ ataxia and neuropathy. | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed | ||
| Encephalopathy | Found in compound w/ W748S, A467T R323H, and M1163R in children w/ progressive encephalopathy | Not found in 200 control alleles | (Kollberg et al., 2006) | PubMed | ||
| Alpers | Found in compound w/ W748S and nt2842_2843insA in children w/ multiple complex deficiencies | Sarzi, et al. 2007 reported 2% (n=50) of patients with multiple respiratory chain deficiency with a 35% decrease of mtDNA were found with the mutation W748S with E1143G. | (Sarzi, et al. 2007) | PubMed | ||
| Alpers with valproate-induced hepatic failure | Found in cis w/ T885S and A467T, and in trans w/ Q879H | (McFarland et al., 2008) | PubMed | |||
| Alpers, Ataxia Neuropathy, and arPEO+ Myocerbrohepatopathy (MCHS) | Found in trans w/ G848S, and in cis w/Q497H-W748S. Also found in trans w/ A467T, and in cis w/ Q497H-W748S. Also in cis w/ E1143 and in trans w/ G737R in MCHS. | (Wong et al., 2008) | PubMed | |||
| PEO and Ataxia | Found in cis w/ G746S and in trans w/ G848S. In a 2nd pt., found in cis w/W748S and in trans w/ G11D and R852C. | (Stewart et al., 2009) | PubMed | |||
| mtDNA depletion | In cis w/ W748S and in trans w/ H1110Y+Q1236H | (Taanman et al., 2008) | PubMed | |||
| Alpers | In cis w/W748S and in trans w/G848S | (Taanman et al., 2008) | PubMed | |||
| Alpers | Found in cis w/ Q497H and W748S, and in trans w/ G848S. | Found in one child with a normal brain MRI. | (Brunetti-Pierri et al., 2008) | PubMed | ||
| Lipodystrophy | Increase susceptibility of HIV pt. treated w/D4T to develop lipodystrophy | (Chiappini, et al., 2009) | PubMed | |||
| PEO, ptosis, polyneuropathy, ataxia, and dysarthria | Found in compound w/ A467T and W748S | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Epilepsy and myoclonic | ar, found w/ A467T | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| Reference # rs2307441 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307441 | PubMed | ||||
| SANDO | Found in trans with A467T and in cis with W748S. Sensory ataxia, dysarthria, and opthalmoplegia. | (Posada et al., 2010) | PubMed | |||
| Alpers | Found in cis with W748S and in trans with R807C in a 1y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Alpers | Found in cis with Q497H and W748S, and in trans with A467T in a 6 y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Alpers | Found in cis with W748S and in trans with G8484S in a 11 mo. old with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| Alpers | Found in cis with W748S and in trans with T914P in a 2.5 y.o. with epilepsy and encephalopathy | 7 of 136 mitochondrial disease Finnish children, and screened against 370 control DNA samples | (Isohanni et al., 2011) | PubMed | ||
| VPA-induced liver toxicity | Found in 2 patients ages 26 and 33 with VPA-induced hepatotoxicity as a heterozygous mutation | A frequency 1.9x10e-4 out of 968 alleles of ethnically matched population controls | (Stewart et al., 2010) | PubMed | ||
| Alpers | Found w/R232H and W748S in a pediatric patient w/mitochondrial encelphalomyopaty, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| Alpers | Found w/M1163R and W748S in a pediatric patient w/mitochondrial encelphalomyopaty, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| MIRAS | Mother and son were homozygous for W748S in cis with E1143, and the unaffected father was heterozygous for W748S in cis with E1143G. Both mother and son had decreased mtDNA and spinocerebellar ataxias with presentation in late 30's and early 40's. | Frequencies in Europe for W748S+E1143G or A467T range from 0.6% in Belgium, 0.8% in Finland, and 2% in Finland | (Palin et al., 2012) | PubMed | ||
| D1145GfsX9 | gagg ins at 3433 /3434 (exon 21) | Seizures | Found in trans w/ L304R in a 12 y.o. with hypotonia and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| R1146C | 3436 c→t (exon 21) | Neutral polymorphism | SNP | 0.6% of 450 individuals | (GeneSNPs, 2004) | PubMed |
| Neutral polymorphism | Found as a heterozygous mutation in a 18 y.o. male with muscle atrophy | 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. | (Gonzalez-Vioque et al., 2006) | PubMed | ||
| Reference # rs2307440 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2307440 | PubMed | ||||
| N1157S | 3470 a→g (exon 21) | ? | Found in trans w/ T251I and P587L in a 9 y.o. w/ no symptoms noted | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| c.3482 +2t>c | 3482 +2t's splice at intron 21 (exon 21) | Alpers | Exon21/Intron21 splice site mutation at a.a. 1161. Found in trans with A467T in a male child w/ infantile hepatocerbral syndrome | (Ferrari et al., 2005) | PubMed | |
| M1163R | 3488 t→g (exon 22) | Liver failure, encephalopathy, and epilepsy | Found as compound in trans with W748S - E1143G | Not found in 200 control alleles | (Kollberg et al., 2006) | PubMed |
| Alpers | Found w/E1143G and W748S in a pediatric patient w/mitochondrial encelphalomyopaty, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) | PubMed | |||
| F1164I | 3490 t→a (exon 22) | PEO | Ar, found in cis with T914P and in trans with Q308H | Not found in 200 Italian controls | (Horvath et al., 2006) | PubMed |
| F1164L | 3492 t→ g or a (exon 22) | Reference # rs62640038 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=62640038 | PubMed | ||
| L1173fsX | 3518 ins gact, fs in exon 22 (exon 22) | Alpers | Compound with A467T | Not found in 300 control chromosomes | (Nguyen et al., 2006) | PubMed |
| Q1175R | 3524 a→g (exon 22) | SNP | Reference # rs188348569 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusID=5428 | PubMed | |
| S1176L | 3527 c→t (exon 22) | PEO | Found as a heterozygous mutation | Lamantea, 2002: Not found in a control group of 100 DNA samples from unrelated Italians | (Lamantea et al., 2002) | PubMed |
| PEO | Found in compound w/with T251I/P587L | (Lamantea and Zeviani, 2004) | PubMed | |||
| D1184L | 3550 g→c (exon 22) | PEO | Found as a compound heterozygote with S998L in a 64 y.o. female with PEO, bilateral ptosis, and encephalopathy. | (Martikainen et al., 2010) | PubMed | |
| C1188R | 3562 t→c (exon 22) | Seizures | Found in trans w/ A467T in a 3 y.o. w/ seizures, hypotonia, and developmentally delayed | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| D1184N | 3550 g→a (exon 22) | PEO and tetraparesis | Compound in trans with N468D | 24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. | (Gonzalez - Vioque et al., 2006) | PubMed |
| Multi-system disorder | Found in compound with R227W in 2 children w/ severe childhood multi-system disorder | de Vries et al. , 2007 identified 1 (4.76%) children out of 21 with a POLG mutation that were known to have a mitochondrial disorder | (de Vries et al., 2007) | PubMed | ||
| Failure to thrive | ar, found in trans w/ S1095R. Aslo, impaired liver functions, deafness, and demyelating sensomotor neuropathy | <0.5% in Dutch population | (Blok and van den Bosch et al., 2009) | PubMed | ||
| R1187W | 3559 c→t (exon 22) | Found in a patient with mitochondrial depletion syndrome and T cell immunodeficiency. Pathogenesis unclear. | Not detected in 100 Turkish control alleles | (Reichenbach et al., 2006) | PubMed | |
| K1191N | 3573 g→t (exon 22) | Alpers | Compound in trans with A467T | Not found in 250 control individuals | (Horvath et al., 2006) | PubMed |
| PEO | Found in trans w/ T251I and P587L in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weakness | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed | ||
| K1191R | 3572 a→g (exon 22) | Myocerebrohepatopathy | In trans with T251I-P587L | (Wong et al., 2008) | PubMed | |
| D1196N | 3586 g→a (exon 22) | Myopathy | In trans w/ G517V | (Wong et al., 2008) | PubMed | |
| T1199X | 3595 ins. a (exon 22) | Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Found with R627Q in a 47 yr. old patient | (Schulte et al., 2009) | PubMed | |
| G1205A | 3614 g→ c (exon 22) | Heterozygous w/ Retinitis pigmentosa, hearing loss, failure to thrive | (Wong et al., 2008) | PubMed | ||
| Y1210fs6X | 3630 ins c (exon 22) | Infantile Hepatocerebral Syndrome | Compound in trans with W748S - E1143G, Mutation causes frame shift to stop at a.a. 1225 | (Ferrari et al., 2005) | PubMed | |
| Alpers | Found in 2 infants in trans w/ W748S | (Spinazzola et al., 2009) | PubMed | |||
| Q1214X | 3640 c→t (exon 22) | PEO | Found in trans w/ S933R in a 60 y.o. w/ PEO, dementia, myopathy, and abnormal muscle histology | 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) | PubMed |
| c.3643+2t>c | 3645 t→c splice variant(exon 22/23) | Alpers | Found in trans w/ A467T | (Roels, et al., 2009) | PubMed | |
| S1230F | 3689 c→t (exon 23) | Neutral polymorphism | <1 % in control populations | (Luoma et al., 2007) | PubMed | |
| Q1236H | 3708 g→t (exon 23) | Neutral polymorphism | 4.0% of 450 individuals | (GeneSNPs, 2004) | PubMed | |
| Neutral polymorphism | Found in 5 PEO patients as a heterozygous mutation | Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians | (Di Fonzo et al., 2003) | PubMed | ||
| Neutral polymorphism | Found in cis with R627Q in trans with A467T in a family w/ ataxia - myopathy and ptosis | (Luoma et al., 2005) | PubMed | |||
| 3711 g→t (exon 23) | Alpers | Found in trans with A467T, and in cis w/ T849H. Also found as a compound w/ R1096C. | (Wong et al., 2008) | PubMed | ||
| mtDNA depletion | In cis w/ H1110Y and in trans w/ E1143G+W748S | (Taanman et al., 2008) | PubMed | |||
| Reference # rs3087374 | http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=3087374 | PubMed | ||||
| VPA induced liver toxicity | Found in 5 patients ages 2 to 47 with VPA-induced hepatotoxicity as a heterozygous mutation | A frequency 1.9x10e-4 out of 968 alleles of ethnically matched population controls | (Stewart et al., 2010) | PubMed | ||
| X1240Q+35a.a. | 3718 t→c +35aa (exon 23) | PEO | Found in trans w/A467T in a 59 y.o. male with arPEO and sensory neuropathy | (Lax et al., 2012b) | PubMed | |
| PEO | Found in trans w/A467T in a 59 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed | |||
| X1240Y+35a.a. | 3720 g→c +35aa (exon 23) | PEO | Found in trans w/A467T in a 42 y.o. female with PEO, ptosis and sensory neuropathy | (Lax et al., 2012a) | PubMed |
