Mitochondrial DNA polymerase γ mutations: An ever expanding molecular and clinical spectrum

Journal of Medical Genetics

Volumn 48, Issue 10, 2011, Pages 669-681

  Tang, Sha ^a   Wang, Jing ^a   Lee, Ni Chung ^b   Milone, Margherita ^c   Halberg, Michelle C ^a   Schmitt, Eric S ^a   Craigen, William J ^a   Zhang, Wei ^a   Wong, Lee Jun C ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^c MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; DNA DIRECTED DNA POLYMERASE GAMMA; OLIGONUCLEOTIDE;

ADOLESCENT; ADULT; ALLELE; ARTICLE; CHILD; CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; COMPARATIVE GENOMIC HYBRIDIZATION; COMPARATIVE STUDY; CONTROLLED STUDY; DNA DETERMINATION; DNA FLANKING REGION; EXON; FEMALE; GENE DELETION; GENE MUTATION; GENETIC CONSERVATION; HUMAN; HUMAN CELL; HUMAN TISSUE; INTRON; LACTIC ACIDEMIA; LIVER DISEASE; MAJOR CLINICAL STUDY; MALE; MISSENSE MUTATION; MITOCHONDRIAL DNA DISORDER; MITOCHONDRIAL GENE; MITOCHONDRIAL GENETICS; MOLECULAR EVOLUTION; MOLECULAR MODEL; MUTATIONAL ANALYSIS; MYOPATHY; NEUROPATHY; PATHOGENESIS; PRESCHOOL CHILD; PRIORITY JOURNAL; PTOSIS; RECESSIVE GENE; SCHOOL CHILD; SEIZURE; SEQUENCE ANALYSIS;

ADOLESCENT; ADULT; AGE OF ONSET; AGED; AGED, 80 AND OVER; ALLELES; CHILD; CHILD, PRESCHOOL; COHORT STUDIES; COMPARATIVE GENOMIC HYBRIDIZATION; DNA-DIRECTED DNA POLYMERASE; FEMALE; GENE FREQUENCY; HUMANS; INFANT; MALE; MIDDLE AGED; MITOCHONDRIAL DISEASES; MODELS, MOLECULAR; MOLECULAR DIAGNOSTIC TECHNIQUES; MUTATION; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; REPRODUCIBILITY OF RESULTS;

EID: 80955158521     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmedgenet-2011-100222     Document Type: Article

References (44)

1. Lee YS, Kennedy WD, Yin YW. Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations. Cell 2009;139:312-24.
2. Szczepanowska K, Foury F. A cluster of pathogenic mutations in the 39-59 exonuclease domain of DNA polymerase gamma defines a novel module coupling DNA synthesis and degradation. Hum Mol Genet 2010;19:3516-29.
3. Chan SS, Copeland WC. DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations. Biochim Biophys Acta 2009;1787:312-19.
4. Milone M, Massie R. Polymerase gamma 1 mutations: clinical correlations. Neurologist 2010;16:84-91.
5. Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC. Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. Hum Mutat 2008;29:E150-72.
6. Winterthun S, Ferrari G, He L, Taylor RW, Zeviani M, Turnbull DM, Engelsen BA, Moen G, Bindoff LA. Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations. Neurology 2005;64:1204-8.
7. Lamantea E, Tiranti V, Bordoni A, Toscano A, Bono F, Servidei S, Papadimitriou A, Spelbrink H, Silvestri L, Casari G, Comi GP, Zeviani M. Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. Ann Neurol 2002;52:211-19.
8. Van Goethem G, Dermaut B, Lofgren A, Martin JJ, Van Broeckhoven C. Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet 2001;28:211-12.
9. Van Goethem G, Martin JJ, Dermaut B, Löfgren A, Wibail A, Ververken D, Tack P, Dehaene I, Van Zandijcke M, Moonen M, Ceuterick C, De Jonghe P, Van Broeckhoven C. Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul Disord 2003;13:133-42.
10. Van Goethem G, Schwartz M, Lofgren A, Dermaut B, Van Broeckhoven C, Vissing J. Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy. Eur J Hum Genet 2003;11:547-9.
11. Deschauer M, Tennant S, Rokicka A, He L, Kraya T, Turnbull DM, Zierz S, Taylor RW. MELAS associated with mutations in the POLG1 gene. Neurology 2007;68:1741-2.
12. Van Goethem G, Luoma P, Rantamaki M, Al Memar A, Kaakkola S, Hackman P, Krahe R, Löfgren A, Martin JJ, De Jonghe P, Suomalainen A, Udd B, Van Broeckhoven C. POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement. Neurology 2004;63:1251-7.
13. Milone M, Brunetti-Pierri N, Tang LY, Kumar N, Mezei MM, Josephs K, Powell S, Simpson E, Wong LJ. Sensory ataxic neuropathy with ophthalmoparesis caused by POLG mutations. Neuromuscul Disord 2008;18:626-32.
14. Hakonen AH, Heiskanen S, Juvonen V, Lappalainen I, Luoma PT, Rantamaki M, Van Goethem G, Löfgren A, Hackman P, Paetau A, Kaakkola S, Majamaa K, Varilo T, Udd B, Kaariainen H, Bindoff LA, Suomalainen A. Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin. Am J Hum Genet 2005;77:430-41.
15. Di Fonzo A, Bordoni A, Crimi M, Sara G, Del Bo R, Bresolin N, Comi GP. POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions. Hum Mutat 2003;22:498-9.
16. Harrower T, Stewart JD, Hudson G, Houlden H, Warner G, O'Donovan DG, Findlay LJ, Taylor RW, De Silva R, Chinnery PF. POLG1 mutations manifesting as autosomal recessive axonal Charcot-Marie-Tooth disease. Arch Neurol 2008;65:133-6.
17. Giordano C, Pichiorri F, Blakely EL, Perli E, Orlandi M, Gallo P, Taylor RW, Inghilleri M, d'Amati G. Isolated distal myopathy of the upper limbs associated with mitochondrial DNA depletion and polymerase gamma mutations. Arch Neurol 2010;67:1144-6.
18. Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee. ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med 2008;10:294-300.
19. Chinault AC, Shaw CA, Brundage EK, Tang LY, Wong LJ. Application of dualgenome oligonucleotide array-based comparative genomic hybridization to the molecular diagnosis of mitochondrial DNA deletion and depletion syndromes. Genet Med 2009;11:518-26.
20. Wong LJ, Dimmock D, Geraghty MT, Quan R, Lichter-Konecki U, Wang J, Brundage EK, Scaglia F, Chinault AC. Utility of oligonucleotide array-based comparative genomic hybridization for detection of target gene deletions. Clin Chem 2008;54:1141-8.
21. Brautbar A, Wang J, Abdenur JE, Chang RC, Thomas JA, Grebe TA, Lim C, Weng SW, Graham BH, Wong LJ. The mitochondrial 13513G/A mutation is associated with Leigh disease phenotypes independent of complex I deficiency in muscle. Mol Genet Metab 2008;94:485-90.
22. Dimmock D, Tang LY, Schmitt ES, Wong LJ. Quantitative evaluation of the mitochondrial DNA depletion syndrome. Clin Chem 2010;56:1119-27.
23. Tzoulis C, Engelsen BA, Telstad W, Aasly J, Zeviani M, Winterthun S, Ferrari G, Aarseth JH, Bindoff LA. The spectrum of clinical disease caused by the A467T and W748S POLG mutations: a study of 26 cases. Brain 2006;129:1685-92.
24. Chan SS, Longley MJ, Naviaux RK, Copeland WC. 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.
25. Gago MF, Rosas MJ, Guimaraes J, Ferreira M, Vilarinho L, Castro L, Carpenter S. SANDO: two novel mutations in POLG1 gene. Neuromuscul Disord 2006;16:507-9.
26. Del Bo R, Bordoni A, Sciacco M, Di Fonzo A, Galbiati S, Crimi M, Bresolin N, Comi GP. Remarkable infidelity of polymerase gammaA associated with mutations in POLG1 exonuclease domain. Neurology 2003;61:903-8.
27. Blok MJ, van den Bosch BJ, Jongen E, Hendrickx A, de Die-Smulders CE, Hoogendijk JE, Brusse E, de Visser M, Poll-The BT, Bierau J, de Coo IF, Smeets HJ. The unfolding clinical spectrum of POLG mutations. J Med Genet 2009;46:776-85.
28. Lim SE, Ponamarev MV, Longley MJ, Copeland WC. Structural determinants in human DNA polymerase gamma account for mitochondrial toxicity from nucleoside analogs. J Mol Biol 2003;329:45-57.
29. Compton AG, Troedson C, Wilson M, Procopis PG, Li FY, Brundage EK, Yamazaki T, Thorburn DR, Wong LJ. Application of oligonucleotide array CGH in the detection of a large intragenic deletion in POLG associated with Alpers Syndrome. Mitochondrion 2011;11:104-7.
30. Vockley J, Rinaldo P, Bennett MJ, Mastern D, Vladutiu GD. Synergistic heterozygosity: disease resulting from multiple partial defects in one or more metabolic pathways. Mol Genet Metab 2000;71:10-18.
31. Galassi G, Lamantea E, Invernizzi F, Tavani F, Pisano I, Ferrero I, Palmieri L, Zeviani M. Additive effects of POLG1 and ANT1 mutations in a complex encephalomyopathy. Neuromuscul Disord 2008;18:465-70.
32. Bolszak M, Anttonen AK, Komulainen T, Hinttala R, Pakanen S, Sormunen R, Herva R, Lehesjoki AE, Majamaa K, Rantala H, Uusimaa J. Digenic mutations in severe myoclonic epilepsy of infancy. Epilepsy Res 2009;85:300-4.
33. Tarutani Y, Shiba H, Iwano M, Kakizaki T, Suzuki G, Watanabe M, Isogai A, Takayama S. Trans-acting small RNA determines dominance relationships in Brassica self-incompatibility. Nature 2010;466:983-6.
34. Brahimi N, Jambou M, Sarzi E, Serre V, Boddaert N, Romano S, de Lonlay P, Slama A, Munnich A, Rötig A, Bonnefont JP, Lebre AS. The first founder DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome. Mol Genet Metab 2009;97:221-6.
35. Barthelemy C, de Baulny HO, Lombes A. D-loop mutations in mitochondrial DNA: link with mitochondrial DNA depletion? Hum Genet 2002;110:479-87.
36. Horvath R, Hudson G, Ferrari G, Futterer N, Ahola S, Lamantea E, Prokisch H, Lochmuller H, McFarland R, Ramesh V, Klopstock T, Freisinger P, Salvi F, Mayr JA, Santer R, Tesarova M, Zeman J, Udd B, Taylor RW, Turnbull D, Hanna M, Fialho D, Suomalainen A, Zeviani M, Chinnery PF. Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Brain 2006;129:1674-84.
37. Lamantea E, Zeviani M. Sequence analysis of familial PEO shows additional mutations associated with the 752C->T and 3527C->T changes in the POLG1 gene. Ann Neurol 2004;56:454-5.
38. Mancuso M, Filosto M, Oh SJ, DiMauro S. A novel polymerase gamma mutation in a family with ophthalmoplegia, neuropathy, and Parkinsonism. Arch Neurol 2004;61:1777-9.
39. Rivera H, Merinero B, Martinez-Pardo M, Arroyo I, Ruiz-Sala P, Bornstein B, Serra-Suhe C, Gallardo E, Marti R, Moran MJ, Ugalde C, Perez-Jurado LA, Andreu AL, Garesse R, Ugarte M, Arenas J, Martin MA. Marked mitochondrial DNA depletion associated with a novel SUCLG1 gene mutation resulting in lethal neonatal acidosis, multi-organ failure, and interrupted aortic arch. Mitochondrion 2010;10:362-8.
40. Stopinska K, Grzybowski T, Malyarchuk BA, Derenko MV, Miscicka-Sliwka D. Optimization of the Y831C mutation detection in human DNA polymerase gamma by allelic discrimination assay. Acta Biochim Pol 2006;53:591-5.
41. Tiangyou W, Hudson G, Ghezzi D, Ferrari G, Zeviani M, Burn DJ, Chinnery PF. POLG1 in idiopathic Parkinson disease. Neurology 2006;67:1698-700.
42. Baruffini E, Lodi T, Dallabona C, Puglisi A, Zeviani M, Ferrero I. Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humans. Hum Mol Genet 2006;15:2846-55.
43. Luoma PT, Eerola J, Ahola S, Hakonen AH, Hellstrom O, Kivisto KT, Tienari PJ, Suomalainen A. Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease. Neurology 2007;69:1152-9.
44. Spelbrink JN, Toivonen JM, Hakkaart GA, Kurkela JM, Cooper HM, Lehtinen SK, Lecrenier N, Back JW, Speijer D, Foury F, Jacobs HT. In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells. J Biol Chem 2000;275:24818-28.