Search
All inquiries, additions to the list, and comments should be made to Bill Copeland.
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Amino Acid Substitution: A467T
cDNA Position: 1399 g→a (exon 7)
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| Disease | Genetics | Frequency | Reference |
| PEO | Found as compound with L304R and R3P in PEO. Also found as a homozygous mutation in a PEO pt. | Three out of 229 control individuals were heterozygous for A467T (allele T frequency 0.6%), while the R3P and L304R mutations were not observed. | (Van Goethem et al., 2001) PubMed |
| PEO | Found as compound with S1104C in a 48 y.o. pt. with PEO | 7 out of 27patients w/sporadic PEO compared to 250 controls individuals had a mutation in POLG | (Agostino et al., 2003) PubMed |
| PEO | Found in compound with G268A | Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians | (Di Fonzo et al., 2003) PubMed |
| PEO | Found as compound with R627Q, L304R or R3P, or G268A | Van Goethem, 2003: absent in 612 Belgian controls. | (Van Goethem et al., 2003a) PubMed |
| MERRF | homozygous mutation in an 18 y.o. patient w/ myoclonus, seizure, and sensory ataxic neuropathy | (Van Goethem et al., 2003b) PubMed |
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| Alpers | Found in compound het with E873stop in Alpers w/ mtDNA depletion | (Naviaux and Nguyen, 2004) PubMed |
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| 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 |
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| (Chan et al., 2005a) PubMed |
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| 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 |
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| 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 |
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| 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 |
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| Ataxia Syndrome | Found as a homozygous mutation in 2 members of the same family with mtDNA deletions | (Winterthun et al., 2005) PubMed |
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| 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 evide | 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 |
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| 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 |
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| 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 |
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| 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 homoz | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed |
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| 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 |
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| Alpers | Found in trans w/T914P | (Taanman et al., 2008) PubMed |
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| Alpers | Found in trans w/ R574W | (Spinazzola et al., 2009) PubMed |
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| Alpers | Homozygous | (Spinazzola et al., 2009) PubMed |
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| Alpers | Found in trans w/ splice variant c.3643 +2t>c | (Roels, et al., 2009) PubMed |
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| mtDNA depletion | Found in trans w/ G8484S. | (Roels, et al., 2009) PubMed |
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| Prematurity, epilepsy, deafness, retinitis pigmentosa, hemiparesis, and liver failure | Found in trans w/ K925RfsX42 | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Alpers | 5 patients found with a homozygous mutation | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Epilepsy and failure to thrive | Found in trans w/ R227P | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| PEO, exercise intolerance, diabetes, and a 2nd pt. w/ cataract and myopathy | 2 patients; found in trans w/ T251I + P587L | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Alpers | Found in trans w/S305R | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| PEO, ptosis, polyneuropathy, ataxia, and dysarthria | Found in trans w/ W748S and in compound w/ E1143G | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Epilepsy, myoclonus, polyneuropathy, ataxia, and cognitive delay; a 2nd pt. with epilepsy and MELAS-like symptoms | Found in trans w/ W748S | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Epilepsy, myoclonus, and developmental delay | Found in trans w/T914P | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Epilepsy, liver failure, occipital strokes, and growth retardation | Found in trans w/ A957P | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Spinocerebellar ataxia, neuro-degeneration, and impaired cognitive functions | ar, 2 patients ages 19 and 48 | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Epilepsy and myoclonus | ar, found with E1143G | <0.5% in a Dutch population | (Blok and van den Bosch et al., 2009) PubMed |
| Cerebellar ataxia, sensory neuropathy, PEO, and dysphagia | Found with W748S in a 43 yr. old patient | (Schulte et al., 2009) PubMed |
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| 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 |
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| 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 |
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| Alpers | Found in trans with G848S | (Hasselmann et al., 2009) PubMed |
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| Hepatocerebral - Alpers symptoms | Found in trans w/P1073L in 2 pt., Psychomotor delay, seizures, liver delay, and gastrointestinal dysmotility. | (Kurt et al., 2010) PubMed |
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| 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 |
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| Alpers | Found as a compound heterozygote w/ a 4.7 kb POLG deletion from intron 14 thru intron 21 w/ a CGH array. Patient had early on set of Alpers and died at the age of 3.5 y.o.. The father carried the A467T mutation, and the mother the deletion. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Compton et al., 2010 and Tang et al., 2011) PubMed |
| Multiple Sclerosis-like illness | Found as a heterozygous mutation w/R275Q in a 63 yr. old. Pt. first diagnosed w/ optic neuritis and MS 33 yrs earlier. Currently, pt. has ragged-red muscle fibers, ptosis, myopathies, PEO, and mtDNA deletions. | (Echaniz-Laguna et al., 2010) PubMed |
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| Alpers | Found in trans w/ P625R in a 1 y.o. with epilepsy and liver failure. | (Baruffini et al., 2011) PubMed |
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| 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 |
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| 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 |
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| Encephalopathy | Found in trans with Q715X in a 5 y.o. pt. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Liver Diseases | Compound heterozygote in cis with W748S | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ T914P in a 3 y.o. with hypotonia, encephalopathy, seizures, and developmentally delayed | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ G848S in an 8 y.o. pt. with seizures, muscle weakness, hypotonia, ataxia, hearing loss, and developmentally delayed. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ G848S in a 1 y.o. pt. with seizures and elevated transaminases, and increased signal basal ganglia | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| SANDO AND PEO | Found in trans w/ W748S in a 54 y.o. with PEO, ptosis, ataxia, neuropathy, and SANDO | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ W748S in a 16 y.o. with seizures, dystonia, choria, neuropathy, and ptosis | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Encephalopathy and ataxia | Found in trans w/ R597W in a 26 y.o. with encephalopathy, ataxis, ptosis, and neuropathy | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/K1050RfsX44 in a 4 y.o. w/ seizures, ataxia, hypotonia, and developmentally delayed. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| PEO | Found as a homozygote in a 46 y.o. pt. w/ ptosis, neuropathy, muscle weakness, and ataxia | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/W748S in an 18 y.o. with ataxia, seizures, dystonia, and optic atrophy. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Ataxia | Found as a homozygote in a 48 y.o. w/ hypotonia, ataxia muscle weakness, and headaches. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ c1443+1g in a 2 y.o. w/ hypotonia, encephalopathy, seizures, cardiomyopathy, and developmentally delayed. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found as a homozygote in a 19 y.o. w/ ataxia, myoclonic seizures, optic atrophy, dysarthria, and developmentally delayed. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| PEO and seizures | Found as a homozygote in a 40 y.o. w/ PEO, ataxia, seizures, and neuropathy | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ L1113P in a 1 y.o. with encephalopathy, seizures, and hepatic failure | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ T914P in a 5 y.o. w/ seizures, hearing loss, and developmentally delayed. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Liver failure | Found in trans w/ S305R in a 1 y.o. with liver failure | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures and liver failure | Found in trans w/ R852C and G11D in a 8 mo. w/ seizures, liver failure, and lactic acidosis. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ F749S in a 6 y.o. w/ seizures | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Hepatic failure | Found in trans w/ S1095R in a 6 mo. w/ hypotonia, liver failure, abnormal muscle histology, and developmentally delayed | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ T914P in a 9 mo. w/ seizures, hypotonia, and developmentally delayed | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures and hepatic failure | Found in trans w/ T914P in a 4 y.o. with liver failure, seizures, and failure to thrive | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ Q1024X in a 2y.o. w/seizures, hearing loss, and hemiparesis | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Found in trans w/ W748S in a 29 y.o. symptoms not noted | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
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| PEO | Found in trans w/ A143V in a 49 y.o. w/ PEO, encephalopathy, ataxia, seizures, neuropathy, hearing loss, and muscle weakness | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Found in trans w/ L304R in a 15 y.o. Symptoms not noted | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
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| Liver failure | Found in trans w/ R807C in a 1 y.o. w/ encephalopathy, liver failure, and lactic acidosis | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ T914P in an 8 mo. w/ seizures, respiratory failure, and an abnormal MRI | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Found in trans w/ F749S in an 8 mo. symptoms not noted | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
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| Seizures and hepatic failure | Found in trans w/ H754Q in a 2 y.o. w/ seizures, hepatic failure, and cerebellar atrophy. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Seizures | Found in trans w/ C1188R in a 3 y.o. w/ seizures, hypotonia, and developmentally delayed | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| VPA induced liver failure | Found in trans w/ G588D in a 2 y.o. w/ VPA induced liver failure | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Found in trans w/ F88L in a 42 y.o. w/ no symptoms noted | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
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| Alpers | Found in trans w/G848S in a 3 y.o. w/seizures, developmentally delayed, and ataxia | (Hunter et al., 2011) PubMed |
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| Alpers | Found in trans w/G848S in a 11 mo. old w/seizures and developmentally delayed | (Hunter et al., 2011) PubMed |
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| Alpers | Found as a homozygous mutation in a 10 y.o. w/seizures and developmentally delayed | (Hunter et al., 2011) PubMed |
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| Alpers | Found in trans w/IVS14+1G>A in a 2 y.o. w/seizures, developmentally delayed, and ataxia | (Hunter et al., 2011) PubMed |
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| Alpers | Found in trans w/R852C in a 5 y.o. w/seizures, ataxia, and developmentally delayed | (Hunter et al., 2011) PubMed |
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| Alpers | Found in trans w/S305R in a 3 y.o. w/seizures and developmentally delayed | (Hunter et al., 2011) PubMed |
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| Alpers | Found in trans w/L966R in a 1 y.o. w/ seizures and developmentally delayed | (Hunter et al., 2011) PubMed |
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| Alpers | Found in trans w/E358A del364X in a 3 y.o. w/seizures, ataxia, and developmentally delayed | (Hunter et al., 2011) PubMed |
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| Alpers | Found in trans w/E358A del364X in a 4 y.o. w/seizures, ataxia, and developmentally delayed | (Hunter et al., 2011) PubMed |
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| Alpers | Found in trans w/L966R in a 1 y.o. w/ seizures and developmentally delayed | (Hunter et al., 2011) PubMed |
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| 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 |
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| 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 |
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| Alpers | Found in trans w/ R574W in 2 pediatric patients w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) PubMed |
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| Alpers | Found in trans w/ G848S in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) PubMed |
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| Alpers | Found in trans w/ G303R in a pediatric patient w/mitochondrial encephalomyopathy, seizures, ataxia, and ophthalmological involvement | (Sofou et al., 2012) PubMed |
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| Alpers | Found in trans w/L966R in a 17 mo. old male with seizures and encephalopathy | (McCoy et al., 2011) PubMed |
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| 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 |
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| Alpers | Found in trans w/R852C in a 21 mo. old female with blindness, anarthria, hypotonia, and epilepsy | (McCoy et al., 2011) PubMed |
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| Alpers | Found in trans w/C418R in a 43 mo. old female with ataxia and seizures | (McCoy et al., 2011) PubMed |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| PEO | Found in trans w/W748S in a 24 y.o. female with arPEO, cerebellar ataxia, and mtDNA deletions | (Lax et al., 2012b) PubMed |
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| PEO | Found in trans w/X1240Q in a 59 y.o. male with arPEO and sensory neuropathy | (Lax et al., 2012b) PubMed |
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| PEO | Found in trans w/X1240Q in a 59 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) PubMed |
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| PEO | Found in trans w/X1240Y in a 42 y.o. Female with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) PubMed |
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| PEO | Found as a homozygous mutation in a 36 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) PubMed |
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| PEO | Found in trans w/W748S in a 47 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) PubMed |
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| PEO | Found in trans w/X1240Y in a 42 y.o. female with PEO, ptosis and sensory neuropathy | (Lax et al., 2012a) PubMed |
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| PEO | Found as a homozygous mutation in a 44 y.o. male with arPEO, ptosis and sensory neuropathy | (Lax et al., 2012a) PubMed |
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| PEO | Found in trans w/W748S in a 48 y.o. male with PEO, ptosis, ataxia and sensory neuropathy | (Lax et al., 2012a) PubMed |
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| Epilepsy | Found in trans w/W748S in a 18 y.o. female with epilepsy, ataxia and sensory neuropathy | (Lax et al., 2012a) PubMed |
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| Epilepsy | Found in trans w/W748S in a 20 y.o.female with epilepsy, ataxia and sensory neuropathy | (Lax et al., 2012a) PubMed |
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| Found in a Chinese population with Parkinsonism at an allelic frequency of 0.028 | 344 Chinese parkinson patients and 144 controls | (Gui et al., 2012) PubMed |
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| PEO | Found in compound with G380D in a 63 yo male with cerebellar ataxia, weakness of lower limbs and cognitive impairment | Found in 160 French cohort of potential POLG patients | (Rouzier et al., 2013) PubMed |
| Alpers | Found in compound with T326fs61X in a 4 yo male with mtDNA depletion | Found in 160 French cohort of potential POLG patients | (Rouzier et al., 2013) PubMed |
| Alpers | Found in compound withT914P in a 15 month female with mtDNA depletion | Found in 160 French cohort of potential POLG patients | (Rouzier et al., 2013) PubMed |
| Epilepsy | Found in compound withW748S in a 17 yo female with axonal neuropathy, cerebellar ataxia, and hyperintensity of rolandic, | Found in 160 French cohort of potential POLG patients | (Rouzier et al., 2013) PubMed |
| Sensorimotor neuropathy | Found as a heterozygous mutation in a 60 yo with ALS-like symptoms and mtDNA deletions. | Found in 160 French cohort of potential POLG patients | (Rouzier et al., 2013) PubMed |
| Encephalopathy | Found as a homozygous mutation in 2 teens both had epilepsy, ataxia, and PEO | (Tzoulis et al., 2013) PubMed |
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| Encephalopathy | Found as a heterozygous mutation with W748S in 2 patients with PEO and ataxia. | (Tzoulis et al., 2013) PubMed |
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| Encephalopathy | Found as a heterozygous mutation with G848S in a patient with epilepsy | (Tzoulis et al., 2013) PubMed |
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| SANDO | Found in trans with T251I and P587L in a female in her 60's with a 5 year history of peripheral neuropathy, blurred vision, unstable gait, and sensory ataxia, dementia, and ophthalmoplegia. | (Lovan et al., 2013) PubMed |
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| Epilepsy | Found with S1104F in a 5 y.o. male. Patient also had myopathy and ataxia. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. | (Sitarz et al., 2014) PubMed |
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| MIRAS | Found with W748S in a 39 y.o. male. Patient also had Ataxia, PEO, and neuropathy. In a study using patient fibroblasts, the cells were unable to up regulate mitochondrial biogenesis when exposed to Valproic acid. | (Sitarz et al., 2014) PubMed |
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| Alpers | Found in a 1 y.o female with c.3626_3629dupGATA, located 14nt before the end of exon 22 resulting in the in a premature stop codon and the skipping of most of exon 22. | (de Camaret et al., 2014) PubMed |
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| SANDO | Found w/W748S in a 37 y.o. female with ataxia, ptosis, seizures, and mtDNA deletions. | (Hanisch et al., 2014) PubMed |
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| SANDO | Found as a homozygous mutation in a 40 y.o. male with ataxia ptosis, and mtDNA deletions. | (Hanisch et al., 2014) PubMed |
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| SANDO | Found w/W748S in a 56 y.o. male with ataxia, ptosis, diabetes and mtDNA deletions. | (Hanisch et al., 2014) PubMed |
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| SANDO | Found w/W748S in a 45 y.o. male with ataxia, ptosis, diabetes and mtDNA deletions. | (Hanisch et al., 2014) PubMed |
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| SANDO | Found w/R627Q in a 50 y.o. male with ataxia, ptosis, diabetes and mtDNA deletions. | (Hanisch et al., 2014) PubMed |
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| Myocerebrohepatopathy | Found w/S1095R in a 4 y.o. boy with hypotonia, failure to thrive, and abnormalities in cranial nerve enhancement | (Horst et al., 2014) PubMed |
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| PEO and encephalopathy | Found as a homozygous mutation in a 15 y.o. w/epilepsy, ataxia, and neuropathy | (Tzoulis et al., 2014) PubMed |
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| PEO and encephalopathy | Found as a homozygous mutation in a 8 y.o. w/epilepsy, ataxia, and neuropathy | (Tzoulis et al., 2014) PubMed |
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| PEO and encephalopathy | Found as a homozygous mutation in a 16 y.o. w/epilepsy, ataxia, and neuropathy | (Tzoulis et al., 2014) PubMed |
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| Encephalopathy | Found w/W748S in a 14 y.o. w/epilepsy, ataxia, and neuropathy | (Tzoulis et al., 2014) PubMed |
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| Encephalopathy | Found w/W748S in a 13 y.o. w/epilepsy, ataxia, and neuropathy | (Tzoulis et al., 2014) PubMed |
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| Encephalopathy | Found w/G303R in a 9 mo. child w/epilepsy and death at 1.1 yrs. | (Tzoulis et al., 2014) PubMed |
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| Encephalopathy | Found w/G303R in a 2 y.o child w/epilepsy, ataxia, and death at 8.0 yrs. | (Tzoulis et al., 2014) PubMed |
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| Encephalopathy | Found w/G848S in a 6 mo. child w/epilepsy and death at 6 mo. | (Tzoulis et al., 2014) PubMed |
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| PEO | Found in compound w/ M919T in a 23 y.o. female patient w/ chronic intestinal pseudo-obstruction, PEO, and ataxia. | In 5 out of 80 patients w/ chronic intestinal pseudo-obstruction | (Amiot et al., 2009) PubMed |
| Alpers | Found as a homozygous mutation in a 3 y.o. female with seizures, cortical degeneration, hepatic microsteatosis,hippocampal sclerosis, and mtDNA depletion and multiple mtDNA mutations. | Carrier frequency in European ancestry of 0.2% to 0.3% | (Rajakulendran et al., 2016) PubMed |
| MEMSA | Found as a homozygous mutation in a 6 y.o. female with encephalitis, occipital lesions, COX-negative muscle fibers and mtDNA deletions and multiple mtDNA mutations. | Carrier frequency in European ancestry of 0.2% to 0.3% | (Rajakulendran et al., 2016) PubMed |
| SANDO | Found as a homozygous mutation in a 20 y.o. male with diplopia, axonal neuropathy, ragged red fibers, COX-negative muscle fibers, mtDNA deletions and multiple mtDNA mutations. | Carrier frequency in European ancestry of 0.2% to 0.3% | (Rajakulendran et al., 2016) PubMed |
| MELAS-like | Found as a homozygous mutation in a 24 y.o. female with axonal sensory motor neuropathy, ragged red fibers, COX-negative muscle fibers, mtDNA deletions and multiple mtDNA mutations. | Carrier frequency in European ancestry of 0.2% to 0.3% | (Rajakulendran et al., 2016) PubMed |
| Migrains, siezures, and ataxia | Found as a compound heterozygote w/ W748S in a 22 y.o. female with epileptic siezures, migrains and ataxia. Her brother presented with siezures at 19 yrs. w/ same mutations. | (Vinjam et al., 2015) PubMed |
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| A study of 68 patients w/ homozygous A467T. Concluded that the clinical presentation was highly variabl, butthat siblings had similar clinical presentations. Attributed the variablitiy to genetic, enviromental, and epigentic factors. | (Neeve et al., 2012) PubMed |
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| MSCA | Found in trans withW748S in a 24 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. | (Tzoulis et al., 2016) PubMed |
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| MSCA | Found in trans with W748ST in a 36 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. | (Tzoulis et al., 2016) PubMed |
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| MSCA | Found in trans with W748ST in a 40 y.o.with encephalopathy, ataxia, and myopathy. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. | (Tzoulis et al., 2016) PubMed |
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| MSCAE | Found in trans with W748S in a16 y.o.with encephalopathy, epilepsy, myopathy, and ataxia. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. | (Tzoulis et al., 2016) PubMed |
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| MSCAE | Found as a homozygous mutation in a 15 y.o.with encephalopathy, epilepsy, SLE, and ataxia. In a study that suggests that dopaminergic neurons are vulnerable to the accumulation of somatic mtDNA damage, and defects of mtDNA replication and repair. | (Tzoulis et al., 2016) PubMed |
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| Alpers | Found as a homozygous mutation in a 3 y.o. girl who had delayed development and epilepsy. | (Rajakulendran et al., 2016) PubMed |
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| MEMSA | Found as a homozygous mutation in a 6 y.o. female with sensory axonal peripheral neuropathy, vision impairment,myoclonus, and COX negative fibers. | (Rajakulendran et al., 2016) PubMed |
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| SANDO | Found as a homozygous mutation in a 20 y.o. male with diplopia,bilateral ptosis, and sensory peripheral neuropathy. | (Rajakulendran et al., 2016) PubMed |
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| "MELAS-like" | Found as a homozygous mutation in a 24 y.o. female with seizure, .deafness, axonal neuropathy, and myopathic weakness. | (Rajakulendran et al., 2016) PubMed |
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| SANDO | Found in trans w/W748S with PEO, deafness, migraines, and depression. | (Bereau et al., 2016) PubMed |
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| SCAE | Found a homozygous mutation with ataxia, seizures, polyneuropathy, and migraine. | (Bereau et al., 2016) PubMed |
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| SANDO | Found in trans w/R597W in a 20 y.o. with ataxia, polyneuropathy, ophthalmoparesis, and dysarthria, | (Bereau et al., 2016) PubMed |
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| PEO | Found in trans with T251I and W748S in a 30 y.o. with muscle weaknes and PEO. | (Bereau et al., 2016) PubMed |
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| SANDO | Found in trans with R1138C in a 35 y.o. with PEO, ataxia, sensory neuropathy, muscle weakness, and Chorea. | (Bereau et al., 2016) PubMed |
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| SCAE | Found in trans with W748S and E1143G in a 36 y.o. with PEO, ataxia, sensory neuropathy, seizures, and migraines. | (Bereau et al., 2016) PubMed |
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| SANDO | Found in trans with L559P in a 50 y.o. with PEO, ataxia, sensory neuropathy, dysarthria, dysphagia, and muscle weakness. | (Bereau et al., 2016) PubMed |
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| PEO | Found in trans w/T251 and P587L in a 56 y.o. with PEO, muscle weakness, and dysphagia. | (Bereau et al., 2016) PubMed |
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| SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) | Found in trans w/T251I and P587L in a 58 y.o. with ataxia, sensory neuropathy, and dysphagia. | (Bereau et al., 2016) PubMed |
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| SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) | Found in trans w/R275Q in a 62 y.o. with ataxia, sensory neuropathy and PEO. | (Bereau et al., 2016) PubMed |
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| SANO (Sensory Ataxic Neuropathy and Ophthalmoparesis) | Found in trans w/T251I and P587L in a 66 y.o. with ataxia, sensory neuropathy, and PEO. | (Bereau et al., 2016) PubMed |
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| SANDO | Found in trans w/G848S with ataxia, sensory neuropathy, dysarthria, and PEO. | (Bereau et al., 2016) PubMed |
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| Gait disturbance | Found w/ W748S in a 26 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities | (Vogel et al., 2017) PubMed |
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| Gait disturbance | Found w/ W748S in a 36 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities | (Vogel et al., 2017) PubMed |
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| Gait disturbance | Found as a heterozygote in a 27 y.o. male with ataxia, speech abnormalities, and swallowing abnormalities | (Vogel et al., 2017) PubMed |
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| Gait disturbance | Found as a heterozygote in a 12 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities | (Vogel et al., 2017) PubMed |
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| Gait disturbance | Found w/W748S in a 49 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities | (Vogel et al., 2017) PubMed |
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| Hypoacusis | Found as a heterozygote in a 20 y.o. male with ataxia, speech abnormalities, and swallowing abnormalities | (Vogel et al., 2017) PubMed |
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| Gait disturbance | Found w/W748S in a 41 y.o. female with ataxia, speech abnormalities, and swallowing abnormalities | (Vogel et al., 2017) PubMed |
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| SANDO | Found in trans w/W748S in a 50 y.o female with multisystem degeneration and cerebellar ataxia. Patient was symptomatic in her 20's which progressed to SANDO. Patient died of sudden cardiac arrest at the age of 50. | (Kirschenbaum et al., 2017) PubMed |
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| Alpers | Found in trans with G848S in two babies | (Hayhurst et al., 2019) PubMed |
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| Seizure, VPA induced liver failure | Found as homozygous in a 20 y.o. male with seizures and VPA induced liver failure.Survived after liver transplantation. | (Bassett et al., 2019) PubMed |
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| MDS | Found in a large cohort study as homozygous or heterzygous in trans with W748S. | Homozygous variant 7% in early onset, 13% Juvenile/adult onset, 5% late onset. Heterzygous variants in trans with W748S 6% in early onset, 23% Juvenile/adult onset, 5% late onset. | (Hikmat et al., 2020) PubMed |
| MTDPSA4 | Found as compound heterozygous in trans with Y282D in a girl who died at the age of 4 years because of MTDPSA4. | (Pauly et al., 2019) PubMed |
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