Polymerase gamma disease through the ages

Developmental Disabilities Research Reviews

Volumn 16, Issue 2, 2010, Pages 163-174

  Saneto, Russell P ^a   Naviaux, Robert K ^b,c  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

DNA; Gene mutation; Genetic inheritance; Mitochondrial disease; POLG spectrum disorders; Polymerase gamma

Indexed keywords

DNA POLYMERASE; PROTEIN POLG; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG; VALPROIC ACID;

ALPERS DISEASE; ATAXIA; AUTOSOMAL RECESSIVE INHERITANCE; CLINICAL FEATURE; DEMOGRAPHY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA REPLICATION; ECOLOGICAL GENETICS; ENVIRONMENTAL FACTOR; EPILEPSY; GENE FUNCTION; GENE MUTATION; GENE REPLICATION; GENE STRUCTURE; GENETIC VARIABILITY; GENOTYPE PHENOTYPE CORRELATION; HUMAN; INFECTION; LIVER FAILURE; MITOCHONDRIAL DNA DEPLETION; MYOCEREBROHEPATOPATHY SYNDROME; MYOCLONUS; MYOPATHY; NEUROPATHY; PHARMACOGENETICS; POLYMERASE GAMMA DISEASE; PREVALENCE; PRIORITY JOURNAL; REVIEW;

EID: 77956251381     PISSN: 19405510     EISSN: 10982779     Source Type: Journal    
DOI: 10.1002/ddrr.105     Document Type: Review

References (117)

1. Aitken H, Gorman G, McFarland R, et al. 2009. Clinical reasoning: blurred vision and dancing feet. Neurology 72:e86-e90.
2. Aknin-Seifer LE, Touraine RL, Lejeune H, et al. 2005. Is the CAG repeat of mitochondrial DNA polymerase gamma (POLG) associated with male infertility? A mult-centgre French study. Hum Repord 20:736-740.
3. Alpers BJ. 1931. Diffuse progressive degeneration of the gray matter of the cerebrum. Arch Neurol Psychiatry 25:469-505.
4. Amaudo E, Dalakas M, Shanske S, et al. 1991. Depletion of muscle mitochondrial DNA in AIDS patiens with zidovudine-induced myopathy. Lancet 337:508-510.
5. Bailey CM, Kasiviswanathan R, Copeland WC. 2009. R964C mutation of DNA polymerase gamma imparts increased stavudine toxicity by decreasing nucleoside analog discrimination and impairing polymerase activity. Antimicrob Agents Chemother 53:2610-2612.
6. Bicknese AR, May W, Hickey WF, Dodson WE. 1992. Early childhood hepatocerebral degeneration misdiagnosed as valproate hepatotoxicity. Ann Neurol 32:767-775.
7. Birky CW. 1994. Relaxed and stringent genomes: why cytoplasmic genes don't obey Mendel's laws. J Hered 85:355-365.
8. Blok MJ, van den Bosch BJ, Jongen E, et al. 2009. The unfolding clinical spectrum of POLG mutations. J Med Genet 46:776-785.
9. Bogenhagen D, Clayton DA. 1977. Mouse L cell mitochondrial DNA molecules are selected randomly for replication throughout the cell cycle. Cell 11:719-727. (Pubitemid 8186397)
10. Bolden A, Noy GP, Weissback A. 1977. DNA polymerase of mitochondria is a gamma-polymerase. J Biol Chem 252:3351-3356.
11. Brown TA, Ceconi C, Tkachuk AN, Custamante C, Clayton DA. 2005. Replication of mitochondrial DNA occurs by strand displacement with alternative light-strand origins, no via a strand-coupled mechanism. Genes Dev 19:2466-2476.
12. Brusco A, Michietlotto C, Gatta V, et al. 2006. The polymorphic polyglutamine repeat in the mitochondrial DNA polymerase gamma gene is not associated with oligozoospermia. J Endocrinol Invest 29:1-4.
13. Calvo S, Jain M, Xie X, et al. 2006. Systematic identification of human mitochondrial disease genes through integrative genomics. Nat Genet 38:576-582.
14. Chan SSL, Copeland WC. 2009. DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations. Biochim Biophys Acta 1787: 312-319.
15. Chan SSL, Longley MJ, Copeland WC. 2006. Modulation of the W748S mutation in DNA polymerase gamma by the E1143G polymorphism in mitochondrial disorders. Hum Mol Genet 15:3473-3483.
16. Chan SSL, Longley MJ, Copeland WC. 2005a. The common A467T mutation in the human mitochondrial DNA polymerase (POLG) compromises catalytic efficiency and interaction with the accessory subunit. JBC 36:31341-31346.
17. Chan SS, Longley MJ, Naviaux RK, et al. 2005b. Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome. DNA Repair 4:1381-1389.
18. th ENMC workshop: polymerase gamma and disorders of mitochondrial DNA synthesis, 21-23 September 2007. Naarden, The Netherlands. Neuromuscul Disord 18:259-267.
19. Chinnery PF, Johnson MA, Wardell TM, et al. 2000. Epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol 48: 188-193.
20. Copeland WC. 2008. Inherited mitochondrial diseases of DNA replication. Ann Rev Med 59:131-146.
21. Dalakas MC, Illa I, Pezeshkpour GH, et al. 1990. Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med 322:1098-1105. (Pubitemid 20149526)
22. Davidzon G, Mancuso M, Ferraris S, et al. 2005. POLG mutations and Alpers syndrome. Ann Neurol 57:921-923.
23. Del Bo, R, Bordoni A, Sciacco M, et al. 2003. Remarkable infidelity of polymerase γA associated with mutations in POLG1 exonuclease domain. Neurology 61:903-908. (Pubitemid 37248642)
24. Deschauer M, Tennant S, Rokicka A, et al. 2007. MELAS associated with mutations in the POLG1 gene. Neurology 68:1741-1742.
25. De Vries MC, Rodenburg RJ, Morava E, et al. 2007. Multiple oxidative phosphorylation deficiencies in severe childhood multi-system disorders due to polymerase gamma (POLG1) mutations. Eur J Pediatr 166:229-234.
26. DiMauro S, Schon EA. 2003. Mitochondrial respiratory-chain diseases. N Engl J Med 348: 2656-2668.
27. Donlin MJ, Patel SS, Johnson KA. 1991. Kinetic partitioning between the exonuclease and polymerase sites in DNA error correction. Biochemistry 30:538-546.
28. Engelsen BA, Tzoulis C, Karlsen B, et al. 2008. POLG1 mutations cause a syndromic epilepsy with occipital lobe predilection. Brain 131:818-828. (Pubitemid 351294723)
29. Fadic R, Russell JA, Vedanarayanan VV, et al. 1997. Sensory ataxic neuropathy as the presenting feature of a novel mitochondrial disease. Neurology 49:239-245.
30. Farge G, Pham XH, Holmlund T, Khorostov I, Falkenberg M. 2007. The accessory subunit B of DNA polymerase gamma is required for mitochondrial replisome function. Nuclei Acids Res 35:902-911.
31. Ferrari G, Lamantea E, Donati A, et al. 2005. Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-γ A. Brain 128:723-731.
32. Filosto M, Mancuso M, Nishigaki Y, et al. 2003. Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma. Arch Neurol 60:1279-1284.
33. Gallo RC. 1971. Synthesis and metabolism of DNA and DNA precursors by human normal and leukemic leukocytes. A summary of recent information. Acta Haematol 45: 136-158.
34. Gonzalez-Vioque E, Bazquez A, Ferandez-Moreira D, et al. 2006. Association of novel POLG mutations and multiple mitochondrial DNA deletions with variable clinical phenotypes in a Spanish population. Arch Neurol 63:107-111. (Pubitemid 43063868)
35. Gramstad A, Bindoff LA, Lillebo A, et al. 2009. Neuropsychological performance in patients with POLG1 mutations and the syndrome of mitochondrial spinocerebellar ataxia and epilepsy. Epilepsy Behav 16:172-174.
36. Graziewicz MA, Longley MJ, Copeland WC. 2006. DNA polymerase gamma in mitochondrial DNA replication and repair. Chem Rev 106:383-405. (Pubitemid 43316563)
37. Graziewicz MA, Longley MJ, Bienstock RJ, et al. 2004. Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophythalmoplegia. Nat Struct Mol Biol 11:770-776.
38. Hakonen AH, Davidzon G, Salemi R, et al. 2007. 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 15: 779-783.
39. Hakonen AH, Heiskanen S, Juvonen V, et al. 2005. Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin. Am J Hum Genet 77:430-441.
40. Harding RN, Alsanjari N, Smith SJM, et al. 1995. Progressive neuronal degeneration of childhood with liver-disease (Alpers-disease) presenting in young adults. J Neurol Neurosurg Psychiatry 58:320-325.
41. Harding RN. 1990. Progressive neuronal degeneration of childhood with liver disease (Alpers-Huttenlocher syndrome): a personal review. J Child Neurol 5:273-287.
42. Harrower T, Stewart JD, Hudson G, et al. 2008. POLG1 mutations manifesting as autosomal recessive axonal Charcot-Marie-Tooth disease. Arch Neurol 65:133-136.
43. Herskowitz A, Willoughby SB, Baughman KL, et al. Cardiomyopathy associated with antiretroviral therapy in patients with HIV infection: a report of six cases. Ann Intern Med 116:311-313.
44. Hirano M, Silvestri G, Blake DM, et al. 1994. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder. Neurology 44:721-727.
45. Hisama FM, Mancuso M, Filosto M, et al. 2005. Progressive external ophthalmoplegia: a new family with tremor and peripheral neuropathy. Am J Med Genet A 135:217-219. (Pubitemid 40769978)
46. Holt IJ.. 2009. Mitochondrial DNA replication and repair: all a flap. Trends in Biochem Sci 34:358-365.
47. Horvath R, Hudson G, Ferrari G, et al. 2006. Phenotypic spectrum associated with mutations of the mitochondrial polymerase γ gene. Brain 129:1674-1684.
48. Hudson G, Chinnery PF. 2006a. Mitochondrial DNA polymerase-gamma and human disease. Hum Mol Genet 15:R244-R252. (Pubitemid 44446800)
49. Hudson G, Deschauer M, Taylor RW, et al. 2006b. POLG1, C10ORF2, and ANT1 mutations are uncommon in sporadic progressive external ophthalmoplegia with multiple mitochondrial DNA deletions. Neurology 66:1439-1441.
50. Jensen M, Leffers H, Petersen JH, et al. 2004. Frequent polymorphism of the mitochondrial DNA polymerse gamma gene (POLG) in patients with normal spermiograms and unexplained subfertility. Hum Reprod 19:65-70.
51. Johnson AA, Johnson KA. 2001. Exonuclease proofreading by human mitochondrial DNA polymerase. J Biol Chem 276:38097-38107. (Pubitemid 37384063)
52. Kakuda TN. 2000. Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin Ther 22:685-708.
53. Kalf GF, Ch'ih JJ. 1968. Purification and properties of deoxyribonucleic acid polymerase from rat liver mitochondria. J Biol Chem 243:4904-4916.
54. Kaguni LS. 2004. DNA polymerase gamma, the mitochondrial replicase. Ann Rev biochem 73:293-320.
55. Kasiviswanathan R, Longley M, Chan SSL, Copeland WC. 2009. Disease mutations in the human mitochondrial DNA polymerase thumb subdomain impart severe defects in mitochondrial DNA replication. J Biol Chem 284:19501-19510.
56. Kollberg G, Moslemi A-R, Darin N, et al. 2006. POLG1 mutations associated with progressive encephalopathy in childhood. J Neuropathol Exp Neurol 65:758-768.
57. Kollberg G, Jansson M, Perez-Bercoff A, et al. 2005. Low frequency of mtDNA point mutations in patients with PEO associated with POLG1 mutations. Eur J Hum Genet 13:463-469. (Pubitemid 40520937)
58. Krausz C, Guarducci E, Becherini L, et al. 2004. The clinical significance of the POLG gene polymorphism in male infertility. J Clin Endocrinol Metab 89:4292-4297.
59. Lamantea E, Tiranti V, Bordoni A, et al. 2002. Mutations of mitochondrial DNA polymerase gamma are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. Ann Neurol 52:211-219.
60. Lecrenier N, Van Der Bruggen P, Foury F. 1997. Mitochondrial DNA polymerases from yeast to man: a new family of polymerases. Gene 185:147-152. (Pubitemid 27068023)
61. Lee Y-S, Kennedy WD, Yin YW. 2009. Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations. Cell 139:312-324.
62. Lee HR, Johnson KA. 2006. Fidelity of nucleotide incorporation by human mitochondrial DNA polymerase. J Biol Chem 276:38090-38096.
63. Lim SE, Ponamarev MV, Longley MJ, et al. 2003. Structural determinants in human DNA polymerase gamma account for mitochondrial toxicity from nucleoside analogs. J Mol Biol 329:45-57.
64. Luoma PT, Eerola J, Ahola AH, et al. 2007. Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease. Neurology 69:1152-1159.
65. Luoma PT, Luo N, Loscher WN, et al. 2005. Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome. Hum Mol Genet 14:1907-1920.
66. Luoma P, Melberg A, Rinne JO, et al. 2004. Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet 364:875-882.
67. Malyarchuk BA, Papuga M, Grzybowski T, et al. 2005. Low variability of the POLG (CAG)n repeat in north Eurasian populations. Hum Biol 77:355-365. (Pubitemid 41513030)
68. Meyer RR, Simpson MV. 1968. DNA biosynthesis in mitochondria: partial purification of a distinct DNA polymerase from isolated rat liver mitochondria. PNAS 61:130-137.
69. Milone M, Brunetti-Perri N, Tang LY, et al. 2008. Sensory ataxic neuropathy with ophthalmoparesis caused by POLG mutations. Neuromuscul Disord 18:626-632.
70. Murakami E, Feng JY, Lee H, et al. 2003. Characterization of novel reverse transcriptase and other RNA-associated catalytic activities by human DNA polymerase gamma: importance in mitochondrial DNA replication. J Biol Chem 278:36403-36409.
71. Naviaux RK, Barshop BA, Nyhan WL, Haas RH. 1996. Reverse transcription and the bipotential replication of mitochondrial DNA. Ann Neurol 40:29A.
72. Naviaux RK, Nguyen KV. 2004. POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann Neurol 55:706-712.
73. Naviaux RK, Nyhan WL, Barshop BA, et al. 1999. Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers' syndrome. Ann Neurol 45:54-58.
74. Nguyen KV, Shariel FS, Chan SSL, et al. 2006. Molecular diagnosis of Alpers syndrome. J Hepatol 45:108-116.
75. Nowak R, Zub R, Skoneczna I, et al. 2005. CAG repeat polymorphism in the DNA polymerase (gamma) gene in a Polish population: an association with testicular cancer risk. Ann Oncol 16:2111-1212. (Pubitemid 41418330)
76. Pagnamenta A, Taanman J-W, Wilson CJ, et al. 2006. Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma. Hum Reprod 21:2467-2473.
77. Ponamarev MJ, Longley MJ, Nguyen D, Kunkel TA, Copeland WC. 2002. Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes erro-prone DNA synthesis. J Biol Chem 277:15225-15228. (Pubitemid 34967780)
78. Richman DD, Fischl MA, Grieco MH, et al. 1987. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med 317:192-197.
79. Robberson DL, Kasamatsu H, Vinograd J. 1972. Replication of mitochondrial DNA. Circular replicative intermediates in mouse L cells. Proc Natl Acad Sci USA 69:737-741.
80. Ropp PA, Copeland WC. 1996. Cloning and characterization of the human mitochondrial DNA polymerase. DNA polymerase gamma. Genomics 36:449-458.
81. Rovio AT, Marchington DR, Donat S, et al. 2001. Mutations at the mitochondrial. DNA polymerase (POLG) locus associated with male infertility. Nat Genet 29:261-262.
82. Rubio-Gozalbo ME, Dijkman KP, van den Heuvel LP, et al. 2000. Clinical differences in patients with mitochondriocytopathies due to nuclear versus mitochondrial DNA mutations. Hum Mutat 15:522-532.
83. Sanderson S, Green A, Preece MA, et al. 2006. The incidence of inherited metabolic disorders in the West Midlands, UK. Arch Dis Child 91:896-899. (Pubitemid 44690201)
84. Saneto RP, Lee I-C, Koenig MK, et al. 2010. POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders. Seizure 19:140-146.
85. Saneto RP, Friedman S, Shaw DWW. 2008. Neuroimaging in mitochondrial disease. Mitochondrion 8:396-413.
86. Scaglia F, Sutton VR, Bodamer OA, et al. 2001. Mitochondrial DNA depletion associated with partial complex II and IV deficiencies and 3-methylglutaconic aciduria. J Child Neurol 16:136-138.
87. Schaefer AM, McFarland R, Blakely EL, et al. 2008. Prevalence of mitochondrial DNA disease in adults. Ann Neurol 63:35-39. (Pubitemid 351240549)
88. Schaefer AM, Taylor RW, Turnbull DM, et al. 2004. The epidemiology of mitochondrial disorders-past, present and future. Biochim Biophys Acta 1659:115-120.
89. Smeitink JA, Zeviani M, Turnbull DM, et al. 2006. Mitochondrial medicine: a metabolic perspective on the pathology of oxidative phosphorylation disorders. Cell Metabol 3: 9-13.
90. Smeitink J, van den Heuvel L, DiMauro S. 2001. The genetics and pathology of oxidative phosphorylation. Nat Rev Genet 2:342-352.
91. Spelbrink JN, Toivonen JM, Hakkaart GA, et al. 2000. In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells. J Biol Chem 275:24818-24828.
92. Spinazzola A, Zeviani M. 2009. Disorders from perturbations of nuclear-mitochondrial intergenomic cross-talk. J Intern Med 265:174-192.
93. Stewart JD, Tennant S, Powell H, et al. Novel POLG1 mutations associated with neuromuscular and liver phenotypes in adults and children. J Med Genet 46:209-214.
94. Suomalainen A, Majander P, Wallin M, et al. 1997. Autosomal dominant progressive external ophthalmoplegia with multiple deletions of mtDNA: clinical biochemical, and molecular genetic features of the 10q-linked disease. Neurology 48:1244-1253.
95. Taanman J-W, Rahman S, Pagnamenta AT, et al. 2009. Analysis of mutant DNA polymerase γ in patients with mitochondrial DNA depletion. Hum Mut 30:248-254.
96. Thorburn DR, Dahl HHM. 2001. Mitochondrial disorders: genetics, counseling, prenatal diagnosis and reproductive options. Am J Med Genet 106:102-114. (Pubitemid 32601622)
97. Tulinius MH, Benti R, Castelli E, et al. 1991a. Mitochondrial encephalomyopathies in childhood. I. Biochemical and morphologic investigations. J Pediatr 119:242-250.
98. Tulinius MH, Hagne I. 1991b. EEG findings in children and adolescents with mitochondrial encephalomyopathies: a study of 25 cases. Brain and Develop 13:167-173.
99. Tzoulis C, Engelsen BA, Telstad W, et al. 2006. The spectrum of clinical disease caused by the A467T and W748S POLG mutations: a study of 26 cases. Brain 129:1685-1692.
100. Ulmer S, Flemming K, Hahn A, Stephani U, Jansen O. 2002. Detection of acute cytotoxic changes in progressive neuronal degeneration of childhood with liver disease (Alpers-Huttenlocher syndrome) using diffusion-weighted MRI and MR spectroscopy. J Comput Assist Tomogr 26:641-646.
101. Uusimaa J, Hinttala R, Rantala H, et al. 2008. Homozygous W748S mutation in the POLG1 gene in patients with juvenile-onset Alpers syndrome and status epilepticus. Epilepsia 49:1038-1045.
102. Van Goethem G, Luoma P, Rantamaki M, et al. 2004. POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement. Neurology 63:1251-1257.
103. Van Goethem G, Martin JJ, Dermaut B, et al. 2003a. Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul Disord 13:133-142.
104. Van Goethem G, Mercelis R, Lofgren L, et al. 2003b. Patient homozygous for a recessive POLG mutation presents with features of MERRF. Neurology 61:1811-1813. (Pubitemid 38020839)
105. Van Goethem G, Schwartz M, Lofgren A, et al. 2003c. Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy. Eur J Hum Genet 11:547-549.
106. Van Goethem G, Dermaut B, Lofgren A, et al. 2001. Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet 28: 211-212. (Pubitemid 32626018)
107. Wallace DC. 2005. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Ann Rev Genet 39:359-407.
108. Weiss MD, Saneto RP. 2010. Sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) in late life due to compound heterozygous POLG mutations. Muscle Nerve 41:882-885.
109. Weissbach A, Baltimore D, Bollum F, Gallo R, Korn D. 1975. Nomenclature of eukaryotic DNA polymerases. Science 190:401-402.
110. Winterthun S, Ferrari G, He L, et al. 2005. Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations. Neurology 64: 1204-1208.
111. Wolf NI, Rahman S, Schmitt B, et al. 2009. Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI findings. Epilepsia 50:1596-1607.
112. Wong L-JC, Naviaux RK, Brunetti-Pierri N, et al. 2008. Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. Hum Mut 29:E150-E172.
113. Wortmann SB, Rodenburg RJT, Jonckheeere A, et al. 2009. Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy. Brain 132:136-146.
114. Yakubovskaya E, Chen Z, Carrodeguas JA, et al. 2006. Functional human mitochondrial DNA polymerase gamma forms a heterotrimer. J Biol Chem 281:374-382. (Pubitemid 43671198)
115. Yamanaka H, Gatanaga H, Kosalaraksa P, et al. 2007. Novel mutation of human DNA polymerase gamma associated with mitochondrial toxicity induced by anti-HIV treatment. J Infect Dis 195:1419-1425.
116. Yarchoan R, Mitsuya H, Myers CE, et al. 1989. Clinical pharmacology of 3′-azido-2′,3′-dideoxythymidine (zidovudine) and related dideoxynucleosides. N Engl J Med 321: 726-738. (Pubitemid 19239705)
117. Zeviani M, Di Donato S. 2004. Mitochondrial disorders. Brain 127:2153-2172.