POLG

Summary

Gene Symbol: POLG
Description: DNA polymerase gamma, catalytic subunit
Alias: MDP1, MIRAS, MTDPS4A, MTDPS4B, PEO, POLG1, POLGA, SANDO, SCAE, DNA polymerase subunit gamma-1, PolG-alpha, mitochondrial DNA polymerase catalytic subunit, polymerase (DNA directed), gamma, polymerase (DNA) gamma, catalytic subunit, truncated mitochondrial DNA polymerase gamma catalytic subunit
Species: human
Products:     POLG

Top Publications

  1. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink J, Rovio A, Bruder C, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004;429:417-23 pubmed
    ..question experimentally by creating homozygous knock-in mice that express a proof-reading-deficient version of PolgA, the nucleus-encoded catalytic subunit of mtDNA polymerase...
  2. Van Goethem G, Luoma P, Rantamaki M, Al Memar A, Kaakkola S, Hackman P, et al. POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement. Neurology. 2004;63:1251-7 pubmed
    To identify POLG mutations in patients with sensory ataxia and CNS features. The authors characterized clinical, laboratory, and molecular genetic features in eight patients from five European families...
  3. Hudson G, Schaefer A, Taylor R, Tiangyou W, Gibson A, Venables G, et al. Mutation of the linker region of the polymerase gamma-1 (POLG1) gene associated with progressive external ophthalmoplegia and Parkinsonism. Arch Neurol. 2007;64:553-7 pubmed
    ..progressive external ophthalmoplegia 1 (PEO1), adenine nucleotide translocator 1 (ANT1), and polymerase gamma-1 (POLG1) genes. We identified 3 novel heterozygous POLG1 substitutions in the same family...
  4. Kurt B, Jaeken J, Van Hove J, Lagae L, Löfgren A, Everman D, et al. A novel POLG gene mutation in 4 children with Alpers-like hepatocerebral syndromes. Arch Neurol. 2010;67:239-44 pubmed publisher
    To describe a novel POLG missense mutation (c.3218C>T; p.P1073L) that, in association with 2 previously described mutations, caused an Alpers-like hepatocerebral syndrome in 4 children. Genotype-phenotype correlation...
  5. Stumpf J, Copeland W. Mitochondrial DNA replication and disease: insights from DNA polymerase γ mutations. Cell Mol Life Sci. 2011;68:219-33 pubmed publisher
    DNA polymerase γ (pol γ), encoded by POLG, is responsible for replicating human mitochondrial DNA...
  6. Szczepanowska K, Foury F. A cluster of pathogenic mutations in the 3'-5' exonuclease domain of DNA polymerase gamma defines a novel module coupling DNA synthesis and degradation. Hum Mol Genet. 2010;19:3516-29 pubmed publisher
  7. Chen X, Goudsmit J, van der Kuyl A. Lack of correlation between length variation in the DNA polymerase gamma gene CAG repeat and lactic acidosis or neuropathy during antiretroviral treatment. AIDS Res Hum Retroviruses. 2002;18:531-4 pubmed
    ..To investigate whether CAG repeat expansion or mutations in the DNA polymerase gamma (POLG) gene could predispose to peripheral neuropathy or lactic acidosis, we have sequenced part of the second exon of ..
  8. Heidari M, Houshmand M, Hosseinkhani S, Nafissi S, Scheiber Mojdehkar B, Khatami M. Association between trinucleotide CAG repeats of the DNA polymerase gene (POLG) with age of onset of Iranian Friedreich's ataxia patients. Neurol Sci. 2008;29:489-93 pubmed publisher
    ..As mitochondrial DNA (mtDNA) copy number has been decreased in FRDA cells and mtDNA polymerase (POLG) is involved in the replication of mtDNA, we searched a trinucleotide CAG repeat length of this enzyme...
  9. Melberg A, Nennesmo I, Moslemi A, Kollberg G, Luoma P, Suomalainen A, et al. Alzheimer pathology associated with POLG1 mutation, multiple mtDNA deletions, and APOE4/4: premature ageing or just coincidence?. Acta Neuropathol. 2005;110:315-6 pubmed

More Information

Publications79

  1. Davidzon G, Mancuso M, Ferraris S, Quinzii C, Hirano M, Peters H, et al. POLG mutations and Alpers syndrome. Ann Neurol. 2005;57:921-3 pubmed
    ..early onset, has been associated with mitochondrial DNA (mtDNA) depletion and mutations in polymerase gamma gene (POLG)...
  2. Spelbrink J, Toivonen J, Hakkaart G, Kurkela J, Cooper H, Lehtinen S, et al. In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells. J Biol Chem. 2000;275:24818-28 pubmed
    The human gene POLG encodes the catalytic subunit of mitochondrial DNA polymerase, but its precise roles in mtDNA metabolism in vivo have not hitherto been documented...
  3. Galassi G, Lamantea E, Invernizzi F, Tavani F, Pisano I, Ferrero I, et al. Additive effects of POLG1 and ANT1 mutations in a complex encephalomyopathy. Neuromuscul Disord. 2008;18:465-70 pubmed publisher
    ..or recessive progressive external ophthalmoplegia (PEO) to juvenile-onset spino-cerebellar ataxia and epilepsy (SCAE) or infantile Alpers-Huttenlocher syndrome...
  4. Lee H, Helquist S, Kool E, Johnson K. Base pair hydrogen bonds are essential for proofreading selectivity by the human mitochondrial DNA polymerase. J Biol Chem. 2008;283:14411-6 pubmed
    ..The enzyme may use the alignment and prevention of fraying provided by proper hydrogen bonding and minor groove hydrogen bonding interactions as critical criteria for correct base pair recognition. ..
  5. Nguyen K, Sharief F, Chan S, Copeland W, Naviaux R. Molecular diagnosis of Alpers syndrome. J Hepatol. 2006;45:108-16 pubmed
    ..Mutations in the gene for the mitochondrial DNA polymerase (POLG) have recently been shown to cause this disorder.
  6. Lewis W, Day B, Kohler J, Hosseini S, Chan S, Green E, et al. Decreased mtDNA, oxidative stress, cardiomyopathy, and death from transgenic cardiac targeted human mutant polymerase gamma. Lab Invest. 2007;87:326-35 pubmed
    b>POLG is the human gene that encodes the catalytic subunit of DNA polymerase gamma (Pol gamma), the replicase for human mitochondrial DNA (mtDNA)...
  7. Rantamaki M, Luoma P, Virta J, Rinne J, Paetau A, Suomalainen A, et al. Do carriers of POLG mutation W748S have disease manifestations?. Clin Genet. 2007;72:532-7 pubmed
    Mitochondrial recessive ataxia syndrome (MIRAS) is a common cause of autosomal recessive juvenile- or adult-onset ataxia, at least in Scandinavia. MIRAS patients are homozygous or compound heterozygous for POLG mutations W748S and A467T...
  8. Luoma P, Melberg A, Rinne J, Kaukonen J, Nupponen N, Chalmers R, et al. Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet. 2004;364:875-82 pubmed
    Mutations in the gene encoding mitochondrial DNA polymerase gamma (POLG), the enzyme that synthesises mitochondrial DNA (mtDNA), have been associated with a mitochondrial disease-autosomal dominant or recessive progressive external ..
  9. Uusimaa J, Hinttala R, Rantala H, Päivärinta M, Herva R, Roytta M, et al. Homozygous W748S mutation in the POLG1 gene in patients with juvenile-onset Alpers syndrome and status epilepticus. Epilepsia. 2008;49:1038-45 pubmed publisher
    ..Numerous mutations in the POLG1 gene have been detected recently in patients with various phenotypes including a classic infantile-onset Alpers-..
  10. Tiangyou W, Hudson G, Ghezzi D, Ferrari G, Zeviani M, Burn D, et al. POLG1 in idiopathic Parkinson disease. Neurology. 2006;67:1698-700 pubmed
    We studied POLG1 in 140 UK patients with idiopathic Parkinson disease (PD) and 279 Italian patients with PD and compared them to a UK control group (n = 207) and an Italian control group (n = 285)...
  11. Engelsen B, Tzoulis C, Karlsen B, Lillebø A, Laegreid L, Aasly J, et al. POLG1 mutations cause a syndromic epilepsy with occipital lobe predilection. Brain. 2008;131:818-28 pubmed publisher
    The epileptic semiology of 19 patients (from 15 families) with mitochondrial disease due to mutations in the POLG1 gene is presented. The patients were either homozygous for the 1399G > A (p.A467T) or 2243G > C (p...
  12. Naviaux R, Nguyen K. POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann Neurol. 2004;55:706-12 pubmed
    ..mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease...
  13. McHugh J, Lonergan R, Howley R, O Rourke K, Taylor R, Farrell M, et al. Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) in a sibling pair with a homozygous p.A467T POLG mutation. Muscle Nerve. 2010;41:265-9 pubmed publisher
    ..A467T mutation of the polymerase gamma (POLG) gene. The clinical course in both subjects was progression to severe disability...
  14. Tzoulis C, Tran G, Schwarzlmüller T, Specht K, Haugarvoll K, Balafkan N, et al. Severe nigrostriatal degeneration without clinical parkinsonism in patients with polymerase gamma mutations. Brain. 2013;136:2393-404 pubmed publisher
    ..The additional presence of both thalamic and cerebellar dysfunction in our patients suggested that these may play a role in counteracting the effects of basal ganglia dysfunction and prevent the development of clinical parkinsonism. ..
  15. Van Goethem G, Dermaut B, Lofgren A, Martin J, Van Broeckhoven C. Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet. 2001;28:211-2 pubmed
    ..pedigree and identified a heterozygous mutation (Y955C) in the polymerase motif B of the mtDNA polymerase gamma (POLG). We identified three additional POLG missense mutations compatible with recessive PEO In two nuclear families...
  16. Filosto M, Mancuso M, Nishigaki Y, Pancrudo J, Harati Y, Gooch C, et al. Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma. Arch Neurol. 2003;60:1279-84 pubmed
    ..translocator; chromosome 10 open reading frame 2 (C10orf2), encoding Twinkle helicase; and polymerase gamma (POLG), encoding the alpha subunit of polymerase gamma...
  17. Wong L, Naviaux R, Brunetti Pierri N, Zhang Q, Schmitt E, Truong C, et al. Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. Hum Mutat. 2008;29:E150-72 pubmed publisher
    Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults...
  18. Taanman J, Rahman S, Pagnamenta A, Morris A, Bitner Glindzicz M, Wolf N, et al. Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion. Hum Mutat. 2009;30:248-54 pubmed publisher
    ..were compound heterozygous for missense mutations in the gene for the catalytic subunit of DNA polymerase gamma (POLG). Three of the identified mutations, c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p...
  19. Anvret A, Westerlund M, Sydow O, Willows T, Lind C, Galter D, et al. Variations of the CAG trinucleotide repeat in DNA polymerase ? (POLG1) is associated with Parkinson's disease in Sweden. Neurosci Lett. 2010;485:117-20 pubmed publisher
    DNA polymerase gamma (POLG1) is coding for the catalytic subunit of the heterotrimeric mitochondrial DNA polymerase and involved in replication and repair of mitochondrial DNA...
  20. Cohen B, Naviaux R. The clinical diagnosis of POLG disease and other mitochondrial DNA depletion disorders. Methods. 2010;51:364-73 pubmed publisher
    ..as germline mutations in the nuclear genes responsible for mtDNA duplication (the polymerase apparatus including POLG, POLG2 and PEO1) and mtDNA maintenance (those genes that regulate the deoxynucleotide triphosphate pools and other ..
  21. Chan S, Longley M, Copeland W. Modulation of the W748S mutation in DNA polymerase gamma by the E1143G polymorphismin mitochondrial disorders. Hum Mol Genet. 2006;15:3473-83 pubmed
    DNA polymerase gamma (pol gamma) is required for replication and repair of mitochondrial DNA. Over 80 mutations in POLG, the gene encoding the catalytic subunit of pol gamma, have been linked with disease...
  22. Ropp P, Copeland W. Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma. Genomics. 1996;36:449-58 pubmed
    ..The human DNA POL gamma is unique in that the first exon of the gene contains a CAG10 trinucleotide repeat. ..
  23. Ashley N, O Rourke A, Smith C, Adams S, Gowda V, Zeviani M, et al. Depletion of mitochondrial DNA in fibroblast cultures from patients with POLG1 mutations is a consequence of catalytic mutations. Hum Mol Genet. 2008;17:2496-506 pubmed publisher
    ..of 24 children with mutations in the catalytic (alpha) subunit of the mitochondrial DNA (mtDNA) gamma polymerase (POLG1)...
  24. Blomberg Jensen M, Leffers H, Petersen J, Daugaard G, Skakkebaek N, Rajpert De Meyts E. Association of the polymorphism of the CAG repeat in the mitochondrial DNA polymerase gamma gene (POLG) with testicular germ-cell cancer. Ann Oncol. 2008;19:1910-4 pubmed publisher
    A possible association between the polymorphic CAG repeat in the DNA polymerase gamma (POLG) gene and the risk of testicular germ-cell tumours (TGCT) was investigated in this study...
  25. Agostino A, Valletta L, Chinnery P, Ferrari G, Carrara F, Taylor R, et al. Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Neurology. 2003;60:1354-6 pubmed
    To verify the impact of mutations in ANT1, Twinkle, and POLG1 genes in sporadic progressive external ophthalmoplegia associated with multiple mitochondrial DNA (mtDNA) deletions, DNA samples from 15 Italian and 12 British patients were ..
  26. Palin E, Lesonen A, Farr C, Euro L, Suomalainen A, Kaguni L. Functional analysis of H. sapiens DNA polymerase gamma spacer mutation W748S with and without common variant E1143G. Biochim Biophys Acta. 2010;1802:545-51 pubmed publisher
    ..In humans, POLGalpha W748S in cis with an E1143G mutation has been linked to a new type of recessive ataxia, MIRAS, which is the most common inherited ataxia in Finland...
  27. Lamantea E, Tiranti V, Bordoni A, Toscano A, Bono F, Servidei S, et al. Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. Ann Neurol. 2002;52:211-9 pubmed
    ..external ophthalmoplegia with multiple mitochondrial DNA deletions recently has been associated with mutations in POLG1, the gene encoding pol gammaA, the catalytic subunit of mitochondrial DNA polymerase...
  28. Wolf N, Rahman S, Schmitt B, Taanman J, Duncan A, Harting I, et al. Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI features. Epilepsia. 2009;50:1596-607 pubmed publisher
    ..Metabolic disorders frequently underlie this condition, in particular Alpers' disease caused by POLG1 mutations. Status epilepticus may be the first symptom...
  29. Luoma P, Eerola J, Ahola S, Hakonen A, Hellstrom O, Kivistö K, et al. Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease. Neurology. 2007;69:1152-9 pubmed
    ..of parkinsonism, mitochondrial myopathy, and premature amenorrhea in five ethnically distinct families with POLG1 mutations...
  30. Hakonen A, Heiskanen S, Juvonen V, Lappalainen I, Luoma P, Rantamaki M, et al. Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin. Am J Hum Genet. 2005;77:430-41 pubmed
    ..We identified 27 patients with mitochondrial recessive ataxia syndrome (MIRAS) from 15 Finnish families, with a carrier frequency in the general population of 1 : 125...
  31. Jensen M, Leffers H, Petersen J, Nyboe Andersen A, Jørgensen N, Carlsen E, et al. Frequent polymorphism of the mitochondrial DNA polymerase gamma gene (POLG) in patients with normal spermiograms and unexplained subfertility. Hum Reprod. 2004;19:65-70 pubmed
    ..In this study, we explored a possible role of the polymerase gamma (POLG) gene polymorphism, recently reported to be associated with male infertility in some populations...
  32. Tang S, Wang J, Lee N, Milone M, Halberg M, Schmitt E, et al. Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum. J Med Genet. 2011;48:669-81 pubmed publisher
    Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial diseases in children and adults...
  33. Lee Y, Kennedy W, Yin Y. Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations. Cell. 2009;139:312-24 pubmed publisher
  34. Baruffini E, Horvath R, Dallabona C, Czermin B, Lamantea E, Bindoff L, et al. Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model. Mitochondrion. 2011;11:182-90 pubmed publisher
    ..Finally, a significant rescue of extended mutability has been observed for several dominant mutations by treatment with mitochondrial antioxidants. ..
  35. Singh K, Ayyasamy V, Owens K, Koul M, Vujcic M. Mutations in mitochondrial DNA polymerase-gamma promote breast tumorigenesis. J Hum Genet. 2009;54:516-24 pubmed publisher
    ..Polymerase-gamma (POLG) is the only DNA polymerase known to function in human mitochondria...
  36. Wanrooij S, Luoma P, Van Goethem G, Van Broeckhoven C, Suomalainen A, Spelbrink J. Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA. Nucleic Acids Res. 2004;32:3053-64 pubmed
    ..genes, encoding the adenine nucleotide translocator 1, the mitochondrial helicase Twinkle or DNA polymerase gamma (POLG)...
  37. Gonzalez Vioque E, Blazquez A, Fernandez Moreira D, Bornstein B, Bautista J, Arpa J, et al. Association of novel POLG mutations and multiple mitochondrial DNA deletions with variable clinical phenotypes in a Spanish population. Arch Neurol. 2006;63:107-11 pubmed
    ..Both dominant and recessive mutations were reported in the gene encoding the mitochondrial (mt) DNA polymerase gamma (POLG) in patients with progressive external ophthalmoplegia (PEO)...
  38. Chan S, Naviaux R, Basinger A, Casas K, Copeland W. De novo mutation in POLG leads to haplotype insufficiency and Alpers syndrome. Mitochondrion. 2009;9:340-5 pubmed publisher
    Mutations in POLG are a major contributor to pediatric and adult mitochondrial diseases. However, the consequences of many POLG mutations are not well understood...
  39. Chan S, Copeland W. DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations. Biochim Biophys Acta. 2009;1787:312-9 pubmed publisher
    ..Over 160 coding variations in the gene encoding the catalytic subunit of DNA polymerase gamma (POLG) have been identified...
  40. Fan L, Kim S, Farr C, Schaefer K, Randolph K, Tainer J, et al. A novel processive mechanism for DNA synthesis revealed by structure, modeling and mutagenesis of the accessory subunit of human mitochondrial DNA polymerase. J Mol Biol. 2006;358:1229-43 pubmed
  41. Hakonen A, Davidzon G, Salemi R, Bindoff L, Van Goethem G, DiMauro S, et al. Abundance of the POLG disease mutations in Europe, Australia, New Zealand, and the United States explained by single ancient European founders. Eur J Hum Genet. 2007;15:779-83 pubmed
    ..that the DNA polymerase gamma (POLG) W748S mutation, a common cause of mitochondrial recessive ataxia syndrome (MIRAS), has a common ancient founder for all the disease chromosomes in Finland, Norway, United Kingdom, and Belgium...
  42. Chan S, Longley M, Copeland W. The common A467T mutation in the human mitochondrial DNA polymerase (POLG) compromises catalytic efficiency and interaction with the accessory subunit. J Biol Chem. 2005;280:31341-6 pubmed
    Among the nearly 50 disease mutations in the gene for the catalytic subunit of human DNA polymerase gamma, POLG, the A467T substitution is the most common and has been found in 0.6% of the Belgian population...
  43. Balafkan N, Tzoulis C, Müller B, Haugarvoll K, Tysnes O, Larsen J, et al. Number of CAG repeats in POLG1 and its association with Parkinson disease in the Norwegian population. Mitochondrion. 2012;12:640-3 pubmed publisher
    The number of CAG repeats in the mitochondrial DNA-polymerase gamma (POLG1) gene has been associated with Parkinson disease (PD) in some populations...
  44. Atanassova N, Fusté J, Wanrooij S, Macao B, Goffart S, Bäckström S, et al. Sequence-specific stalling of DNA polymerase ? and the effects of mutations causing progressive ophthalmoplegia. Hum Mol Genet. 2011;20:1212-23 pubmed publisher
    ..Our data may also explain why mutations that disturb dATP pools can be especially deleterious for mtDNA synthesis. ..
  45. Rovio A, Marchington D, Donat S, Schuppe H, Abel J, Fritsche E, et al. Mutations at the mitochondrial DNA polymerase (POLG) locus associated with male infertility. Nat Genet. 2001;29:261-2 pubmed
    Human mitochondrial DNA polymerase, encoded by POLG, contains a polyglutamine tract encoded by a CAG microsatellite repeat...
  46. Kasiviswanathan R, Longley M, Chan S, Copeland W. Disease mutations in the human mitochondrial DNA polymerase thumb subdomain impart severe defects in mitochondrial DNA replication. J Biol Chem. 2009;284:19501-10 pubmed publisher
    Forty-five different point mutations in POLG, the gene encoding the catalytic subunit of the human mitochondrial DNA polymerase (pol gamma), cause the early onset mitochondrial DNA depletion disorder, Alpers syndrome...
  47. Winterthun S, Ferrari G, He L, Taylor R, Zeviani M, Turnbull D, et al. Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations. Neurology. 2005;64:1204-8 pubmed
    ..Southern blotting and real time PCR were used to detect deletions of mtDNA and mutations in the POLG gene were identified using a combination of DHPLC and direct DNA sequencing...
  48. Tzoulis C, Neckelmann G, Mørk S, Engelsen B, Viscomi C, Moen G, et al. Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes. Brain. 2010;133:1428-37 pubmed publisher
    ..We suggest therefore that both infantile and later onset polymerase gamma related encephalopathies are part of a continuum...
  49. Mancuso M, Filosto M, Oh S, DiMauro S. A novel polymerase gamma mutation in a family with ophthalmoplegia, neuropathy, and Parkinsonism. Arch Neurol. 2004;61:1777-9 pubmed
    ..Parkinsonism was a prominent clinical feature in this family with autosomal dominant ophthalmoplegia, multiple mitochondrial DNA deletions, and a novel mutation in the polymerase gamma gene. ..
  50. Hopkins S, Somoza A, Gilbert D. Rare autosomal dominant POLG1 mutation in a family with metabolic strokes, posterior column spinal degeneration, and multi-endocrine disease. J Child Neurol. 2010;25:752-6 pubmed publisher
    ..Depending on the location and inheritance, mutations in POLG1, the catalytic subunit, can cause symptoms including severe infantile epilepsy, metabolic strokes, chronic ataxia, ..
  51. Saneto R, Lee I, Koenig M, Bao X, Weng S, Naviaux R, et al. POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders. Seizure. 2010;19:140-6 pubmed publisher
    To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures...
  52. Pagnamenta A, Taanman J, Wilson C, Anderson N, Marotta R, Duncan A, et al. Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma. Hum Reprod. 2006;21:2467-73 pubmed
    ..Recently, mutations in the catalytic subunit of mitochondrial DNA polymerase gamma (POLG) were shown to segregate with POF in families with progressive external ophthalmoplegia (PEO) and multiple large-..
  53. Hudson G, Chinnery P. Mitochondrial DNA polymerase-gamma and human disease. Hum Mol Genet. 2006;15 Spec No 2:R244-52 pubmed
    ..of mitochondrial DNA (mtDNA) is critically dependent upon polymerase-gamma (pol-gamma), encoded by the nuclear gene POLG. Over the last 5 years, it has become clear that mutations of POLG are a major cause of human disease...
  54. Graziewicz M, Bienstock R, Copeland W. The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine. Hum Mol Genet. 2007;16:2729-39 pubmed
    Mitochondrial DNA is replicated and repaired by DNA polymerase gamma (pol gamma), encoded by the POLG gene. The Y955C substitution in POLG leads to autosomal dominant progressive external ophthalmoplegia (PEO) with other severe phenotypes...
  55. Hunter M, Peters H, Salemi R, Thorburn D, Mackay M. Alpers syndrome with mutations in POLG: clinical and investigative features. Pediatr Neurol. 2011;45:311-8 pubmed publisher
    ..Three common polymerase-? mutations, in patients of European descent, can assist with rapid diagnosis, circumventing the need for liver biopsy...
  56. Naviaux R, Nguyen K. POLG mutations associated with Alpers syndrome and mitochondrial DNA depletion. Ann Neurol. 2005;58:491 pubmed
  57. Graziewicz M, Longley M, Copeland W. DNA polymerase gamma in mitochondrial DNA replication and repair. Chem Rev. 2006;106:383-405 pubmed
  58. Yakubovskaya E, Chen Z, Carrodeguas J, Kisker C, Bogenhagen D. Functional human mitochondrial DNA polymerase gamma forms a heterotrimer. J Biol Chem. 2006;281:374-82 pubmed
    ..The structure of pol gamma seems to be variable, ranging from a single catalytic subunit in yeast to a heterodimer in Drosophila and a heterotrimer in mammals. ..
  59. Isohanni P, Hakonen A, Euro L, Paetau I, Linnankivi T, Liukkonen E, et al. POLG1 manifestations in childhood. Neurology. 2011;76:811-5 pubmed publisher
    Mitochondrial DNA polymerase ? (POLG1) mutations in children often manifest as Alpers syndrome, whereas in adults, a common manifestation is mitochondrial recessive ataxia syndrome (MIRAS) with severe epilepsy...
  60. Chan S, Longley M, Naviaux R, Copeland W. Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome. DNA Repair (Amst). 2005;4:1381-9 pubmed
    ..This syndrome has been associated with mutations in POLG, the gene encoding the mitochondrial DNA polymerase (pol gamma)...
  61. Van Goethem G, Martin J, Dermaut B, Lofgren A, Wibail A, Ververken D, et al. Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul Disord. 2003;13:133-42 pubmed
    ..ataxic neuropathy and has the clinical triad of sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO)...
  62. Remes A, Hinttala R, Kärppä M, Soini H, Takalo R, Uusimaa J, et al. Parkinsonism associated with the homozygous W748S mutation in the POLG1 gene. Parkinsonism Relat Disord. 2008;14:652-4 pubmed publisher
    Parkinsonism has been described in patients with mutations in POLG1 gene...
  63. Kollberg G, Moslemi A, Darin N, Nennesmo I, Bjarnadottir I, Uvebrant P, et al. POLG1 mutations associated with progressive encephalopathy in childhood. J Neuropathol Exp Neurol. 2006;65:758-68 pubmed
    We have identified compound heterozygous missense mutations in POLG1, encoding the mitochondrial DNA polymerase gamma (Pol gamma), in 7 children with progressive encephalopathy from 5 unrelated families...
  64. Stewart J, Tennant S, Powell H, Pyle A, Blakely E, He L, et al. Novel POLG1 mutations associated with neuromuscular and liver phenotypes in adults and children. J Med Genet. 2009;46:209-14 pubmed publisher
    The POLG1 gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial DNA replication and repair...
  65. Yakubovskaya E, Lukin M, Chen Z, Berriman J, Wall J, Kobayashi R, et al. The EM structure of human DNA polymerase gamma reveals a localized contact between the catalytic and accessory subunits. EMBO J. 2007;26:4283-91 pubmed
    ..A model for pol gamma is discussed that considers the effects of known mutations in the accessory subunit and the interaction of the enzyme with DNA. ..
  66. Lee H, Helquist S, Kool E, Johnson K. Importance of hydrogen bonding for efficiency and specificity of the human mitochondrial DNA polymerase. J Biol Chem. 2008;283:14402-10 pubmed
    ..Base pair hydrogen bonding contributes at least a third of the energy underlying nucleoside incorporation efficiency and specificity. ..
  67. Euro L, Farnum G, Palin E, Suomalainen A, Kaguni L. Clustering of Alpers disease mutations and catalytic defects in biochemical variants reveal new features of molecular mechanism of the human mitochondrial replicase, Pol ?. Nucleic Acids Res. 2011;39:9072-84 pubmed publisher
    ..represent nearly half of those reported to date, and they are nearly uniformly distributed along the length of the POLG1 gene (Human DNA Polymerase gamma Mutation Database); the majority of them are linked to the most severe form of ..
  68. Woodbridge P, Liang C, Davis R, Vandebona H, Sue C. POLG mutations in Australian patients with mitochondrial disease. Intern Med J. 2013;43:150-6 pubmed publisher
    The nuclear POLG gene encodes the catalytic subunit of DNA polymerase gamma (pol?), the only polymerase involved in the replication and proofreading of mitochondrial DNA...
  69. Eerola J, Luoma P, Peuralinna T, Scholz S, Paisan Ruiz C, Suomalainen A, et al. POLG1 polyglutamine tract variants associated with Parkinson's disease. Neurosci Lett. 2010;477:1-5 pubmed publisher
    A possible role of allelic variation of the mitochondrial DNA polymerase gamma (POLG1) gene in Parkinson's disease (PD) has been suggested...
  70. Blok M, van Den Bosch B, Jongen E, Hendrickx A, De Die Smulders C, Hoogendijk J, et al. The unfolding clinical spectrum of POLG mutations. J Med Genet. 2009;46:776-85 pubmed publisher
    Mutations in the DNA polymerase-gamma (POLG) gene are a major cause of clinically heterogeneous mitochondrial diseases, associated with mtDNA depletion and multiple deletions...