Treatment of hereditary optic neuropathies

Nature Reviews Neurology

Volumn 8, Issue 10, 2012, Pages 545-556

  Newman, Nancy J ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TOCOPHEROL; ARGININE; ASCORBIC ACID; BRIMONIDINE; CARNITINE; CREATINE; CYANOCOBALAMIN; DICHLOROACETIC ACID; FOLIC ACID; IDEBENONE; MANGANESE SUPEROXIDE DISMUTASE; MENADIOL; MINOCYCLINE; MITOCHONDRIAL DNA; PLACEBO; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE SUBUNIT 4; RIBOFLAVIN; THIAMINE; THIOCTIC ACID; UBIDECARENONE; UNCLASSIFIED DRUG; VIRUS VECTOR;

ABSENCE OF SIDE EFFECTS; AMYOTROPHIC LATERAL SCLEROSIS; BLOOD BRAIN BARRIER; CARNITINE DEFICIENCY; CELL NUCLEUS TRANSPLANTATION; DEGENERATIVE DISEASE; DISEASE COURSE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOMINANT OPTIC NEUROPATHY; DRUG EFFICACY; DRUG MECHANISM; DRUG PENETRATION; DRUG TOLERABILITY; GENE EXPRESSION; GENE INSERTION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC COUNSELING; GENETIC TRANSFECTION; GENOTYPE ENVIRONMENT INTERACTION; GLAUCOMA; HEREDITARY OPTIC NEUROPATHY; HUMAN; HUNTINGTON CHOREA; LEBER HEREDITARY OPTIC NEUROPATHY; MOLECULAR PATHOLOGY; MULTIPLE ACYL COA DEHYDROGENASE DEFICIENCY; NONHUMAN; OPTIC NERVE DISEASE; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SPINAL CORD INJURY; SUPPLEMENTATION; SYSTEMATIC REVIEW; TREATMENT DURATION; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; VISUAL ACUITY; VISUAL IMPAIRMENT;

ANIMALS; GENETIC COUNSELING; GENETIC THERAPY; HUMANS; MUTATION; OPTIC ATROPHIES, HEREDITARY; OPTIC ATROPHY, AUTOSOMAL DOMINANT; OPTIC ATROPHY, HEREDITARY, LEBER; TREATMENT OUTCOME;

EID: 84872322750     PISSN: 17594758     EISSN: 17594766     Source Type: Journal    
DOI: 10.1038/nrneurol.2012.167     Document Type: Review

References (119)

1. Carelli, V., Ross-Cisneros, F. N. & Sadun, A. A. Mitochondrial dysfunction as a cause of optic neuropathies. Prog. Retin. Eye Res. 23, 53-89 (2004). (Pubitemid 38177172)
2. Newman, N. J. in Walsh & Hoyt's Clinical Neuro-Ophthalmology 6th edn (eds Miller, N. R. et al.) 465-501 (Williams & Willkins, Baltimore, 2005).
3. Yu-Wai-Man, P., Griffiths, P. G., Hudson, G. & Chinnery, P. F. Inherited optic neuropathies. J. Med. Genet. 46, 145-158 (2009).
4. Fraser, J. A., Newman, N. J. & Biousse, V. The neuro-ophthalmology of mitochondrial disease. Surv. Ophthalmol. 55, 299-334 (2010).
5. Yu-Wai-Man, P., Griffiths, P. G. & Chinnery, P. F. Mitochondrial optic neuropathies-disease mechanisms and therapeutic strategies. Prog. Retin. Eye Res. 30, 81-114 (2011).
6. Sitarz, K. S., Chinnery, P. F. & Yu-Wai-Man, P. Disorders of the optic nerve in mitochondrial cytopathies: new ideas on pathogenesis and therapeutic targets. Curr. Neurol. Neurosci. Rep. 12, 308-317 (2012).
7. Biousse, V. B. & Newman, N. J. in Pediatric Ophthalmology 4th edn (eds Taylor, D. & Hoyt, C. S.) Elsevier Saunders, London [in press].
8. Newman, N. J., Lott, M. T. & Wallace, D. C. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am. J. Ophthalmol. 111, 750-762 (1991).
9. Riordan-Eva, P. et al. The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain 118, 319-337 (1995).
10. Newman, N. J. et al. Prophylaxis for second eye involvement in Leber hereditary optic neuropathy: an open-labeled, nonrandomized multicenter trial of topical brimonidine purite. Am. J. Ophthalmol. 140, 407-415 (2005).
11. Nikoskelainen, E. K. et al. Ophthalmoscopic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology 103, 504-514 (1996). (Pubitemid 26085904)
12. Mackey, D. & Howell, N. A variant of Leber's hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology. Am. J. Hum. Genet. 51, 1218-1228 (1992). (Pubitemid 23001081)
13. Stone, E. M. et al. Visual recovery in patients with Leber's hereditary optic neuropathy and the 11778 mutation. J. Clin. Neuroophthalmol. 12, 10-14 (1992).
14. Oostra, R. J. et al. Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome. J. Med. Genet. 31, 280-286 (1994). (Pubitemid 24127526)
15. Spruijt, L. et al. Influence of mutation type on clinical expression of Leber hereditary optic neuropathy. Am. J. Ophthalmol. 141, 676-682 (2006).
16. Carelli, V. et al. Idebenone treatment in Leber's hereditary optic neuropathy. Brain 134, e188 (2011).
17. Johns, D. R., Smith, K. H. & Miller, N. R. Leber's hereditary optic neuropathy: clinical manifestations of the 3460 mutation. Arch. Ophthalmol. 110, 1577-1581 (1992).
18. Obermaier-Kusser, B. et al. Features of mtDNA mutation patterns in European pedigrees and sporadic cases with Leber hereditary optic neuropathy. Am. J. Hum. Genet. 55, 1063-1066 (1994). (Pubitemid 24334301)
19. Barboni, P. et al. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy. Ophthalmology 112, 120-126 (2005). (Pubitemid 40075330)
20. Barboni, P. et al. Leber's hereditary optic neuropathy with childhood onset. Invest. Ophthalmol. Vis. Sci. 47, 5303-5309 (2006). (Pubitemid 46723779)
21. Ramos Cdo, V. et al. Association of optic disc size with development and prognosis of Leber's hereditary optic neuropathy. Invest. Ophthalmol. Vis. Sci. 50, 1666-1674 (2009).
22. Hoyt, C. S. Autosomal dominant optic atrophy-a spectrum of disability. Ophthalmology 87, 245-251 (1980). (Pubitemid 10130594)
23. Cohn, A. C. et al. The natural history of OPA1-related autosomal dominant optic atrophy. Br. J. Ophthalmol. 92, 1333-1336 (2008).
24. Johnson, R. L. et al. Dominant optic atrophy. Refining the clinical diagnostic criteria in light of genetic linkage studies. Ophthalmology 106, 123-128 (1999).
25. Cohn, A. C. et al. Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations. Am. J. Ophthalmol. 143, 656-662 (2007).
26. Kjer, B. et al. Dominant optic atrophy mapped to chromosome 3q region. II. Clinical and epidemiological aspects. Acta Ophthalmol. Scand. 74, 3-7 (1996).
27. Votruba, M. et al. Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy. Arch. Ophthalmol. 116, 351-358 (1998).
28. Kjer, P. Infantile optic atrophy with dominant mode of inheritance. A clinical and genetic study of 19 Danish families. Acta Ophthalmol. 164 (Suppl. 54), 1-147 (1959).
29. Eliott, D., Traboulsi, E. I. & Maumenee, I. H. Visual prognosis in autosomal dominant optic atrophy (Kjer type). Am. J. Ophthalmol. 115, 360-367 (1993). (Pubitemid 23081079)
30. Puomila, A. et al. Dominant optic atrophy: correlation between clinical and molecular genetic studies. Acta Ophthalmol. Scand. 83, 337-346 (2005). (Pubitemid 40872509)
31. Yu-Wai-Man, P. et al. The prevalence and natural history of dominant optic atrophy due to OPA1 mutations. Ophthalmology 117, 1538-1546 (2010).
32. Cornille, K. et al. Reversible optic neuropathy with OPA1 exon 5b mutation. Ann. Neurol. 63, 667-671 (2008).
33. Yu-Wai-Man, P. et al. Multi-system neurological disease is common in patients with OPA1 mutations. Brain 133, 771-786 (2010).
34. Yu-Wai-Man, P. et al. Pattern of retinal ganglion cell loss in dominant optic atrophy due to OPA1 mutations. Eye 25, 596-602, (2011).
35. Tang, S. et al. Heterozygous mutation of Opa1 in Drosophila shortens lifespan mediated through increased reactive oxygen species production. PLoS ONE 4, e4492 (2009).
36. Costeff, H. et al. A familial syndrome of infantile optic atrophy, movement disorder, and spastic paraplegia. Neurology 39, 595-597 (1989). (Pubitemid 19105784)
37. Ryu, S. W. et al. Optic atrophy 3 as a protein of the mitochondrial outer membrane induces mitochondrial fragmentation. Cell. Mol. Life Sci. 67, 2839-2850 (2010).
38. Hanein, S. et al. TMEM126A, encoding a mitochondrial protein, is mutated in autosomal-recessive nonsyndromic optic atrophy. Am. J. Hum. Genet. 84, 493-498 (2009).
39. Chen, H. C. et al. Mitochondrial fusion is required for mtDNA stability in skeletqal muscle and tolerance of mtDNA mutations. Cell 141, 280-289 (2010).
40. Elachouri, G. et al. OPA1 links human mitochondrial genome maintenance to mtDNA replication and distribution. Genome Res. 21, 12-20 (2011).
41. Dayanithi, G. et al. Characterization of Ca2+ signaling in postnatal mouse retinal ganglioin cells: involvement of OPA1 in Ca2+ clearance. Ophthalmic Genet. 31, 53-65 (2010).
42. de Brito, O. M. & Scorrano, L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456, 605-610 (2008).
43. Trevelyan, A. J. et al. Mitochondrial DNA mutations affect calcium handling in differentiated neurons. Brain 133, 787-796 (2010).
44. Casari, G. et al. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 93, 973-983 (1998). (Pubitemid 28280791)
45. Fortuna, F. et al., Visual system involvement in patients with Friedreichs ataxia. Brain 132, 116-123 (2009).
46. Stemmler, T. L. et al. Frataxin and mitochondrial FeS cluster biogenesis. J. Biol. Chem. 285, 26737-26743 (2010).
47. Pfeffer, G., Majaama, K., Turnbull, D. M., Thorburn, D. & Chinnery, P. F. Treatment for mitochondrial disorders. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD004426. http://dx.doi.org/10.1002/14651858. CD004426.pub3.
48. DiMauro, S. & Mancuso, M. Mitochondrial diseases: therapeutic approaches. Biosci. Rep. 27, 125-137 (2007). (Pubitemid 46940941)
49. Bresolin, N. et al. Clinical and biochemical correlations in mitochondrial myopathies treated with coenzyme Q10. Neurology 38, 392-399 (1988).
50. Bresolin, N. et al. Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial. J. Neurol. Sci. 100, 70-78 (1990).
51. Geromel, V. et al. Coenzyme Q10 and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits. Mol. Genet. Metab. 77, 21-30 (2002). (Pubitemid 35178511)
52. Di Giovanni, S. et al. Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency. Neurology 57, 515-518 (2001). (Pubitemid 32757603)
53. Huang, C. C., Kuo, H. C., Chu, C. C. & Kao, L. Y. Rapid visual recovery after coenzyme Q10 treatment of Leber hereditary optic neuropathy. J. Neuroophthalmol. 22, 66 (2002).
54. Olsen, R. K. et al. ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain 130, 2045-2054 (2007). (Pubitemid 47236622)
55. Tein, I. et al. Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy. Pediatr. Res. 28, 247-255 (1990). (Pubitemid 20262281)
56. Rodriguez, M. C. et al. Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders. Muscle Nerve 35, 235-242 (2007).
57. Tarnopolsky, M. A. The mitochondrial cocktail: rationale for combined nutraceutical therapy in mitochondrial cytopathies. Adv. Drug Deliv. Rev. 60, 1561-1567 (2008).
58. Giorgio, V. et al. The effects of idebenone on mitochondrial bioenergetics. Biochim. Biophys. Acta 1817, 363-369 (2012).
59. Angebault, C. et al. Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration. BMC Res. Notes 4, 557 (2011).
60. Haefeli, R. H. et al. NQO1-dependent redox cycling of idebenone: effects on cellular redox potential and energy levels. PLoS ONE 6, e17963 (2011).
61. Mariotti, C. et al. Idebenone treatment in Friedreich patients: one-year-long randomized placebo-controlled trial. Neurology 60, 1676-1679 (2003). (Pubitemid 36618100)
62. Di Prospero, N. A., Baker, A., Jeffries, N. & Fishbeck, K. H. Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomized, placebo-controlled trial. Lancet Neurol. 6, 878-886 (2007). (Pubitemid 47404985)
63. Lynch, D. R., Perlman, S. L. & Meier, T. A phase 3, double-blind, placebo-controlled trial of idebenone in Friedreich ataxia. Arch. Neurol. 67, 941-947 (2010).
64. Lagedrost, S. J. et al. Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA). Am. Heart J. 161, 639-645 (2011).
65. Imachi, J. & Nishizaki, K. The patients of Leber's optic atrophy should be treated neuro-surgically [Japanese]. Nihon Ganka Kiyo 21, 209-217 (1970).
66. Haroon, M. F. et al. Minocycline, a possible neuroprotective agent in Leber's hereditary optic neuropathy (LHON): studies of cybrid cells bearing 11778 mutation. Neurobiol. Dis. 28, 237-250 (2007). (Pubitemid 350116596)
67. Wong, A. & Cortopassi, G. mtDNA mutations confer cellular sensitivity to oxidant stress that is partially rescued by calcium depletion and cyclosporine A. Biochem. Biophys. Res. Commun. 239, 139-145 (1997). (Pubitemid 27480330)
68. Seaton, T. A., Cooper, J. M. & Schapira, A. H. Cyclosporin inhibition of apoptosis by mitochondrial complex I toxins. Brain Res. 809, 12-17 (1998). (Pubitemid 29003421)
69. Porcelli, A. M. et al. Respiratory complex I dysfunction due to mitochondrial DNA mutations shifts the voltage threshold for opening of the permeability transition pore toward resting levels. J. Biol. Chem. 284, 2045-2052 (2009).
70. Ghelli, A. et al. Protection against oxidant-induced apoptosis by exogenous glutathione in Leber hereditary optic neuropathy cybrids. Invest. Ophthalmol. Vis. Sci. 49, 671-676 (2008).
71. Hudson, G. et al. Identification of an X-chromosome locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. Am. J. Hum. Genet. 77, 1086-1091 (2005). (Pubitemid 41698527)
72. Shankar, S. P. et al. Evidence for a novel X-linked modifier locus for Leber hereditary optic neuropathy. Ophthalmic Genet. 29, 17-24 (2008). (Pubitemid 351431243)
73. Ji, Y. L. et al. Evaluation of the X-linked modifier loci for Leber hereditary optic neuropathy with the G11778A mutation in Chinese. Mol. Vis. 16, 416-424 (2010).
74. Giordano, C. et al. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy. Brain 134, 220-234 (2011).
75. Mashima, Y., Hiida, Y. & Oguchi, Y. Remission of Leber's hereditary optic neuropathy with idebenone. Lancet 340, 368-369 (1992).
76. Cortelli, P. et al. Clinical and brain bioenergetics improvement with idebenone in a patient with Leber hereditary optic neuropathy: a clinical and P-MRS study. J. Neurol. Sci. 148, 25-31 (1997). (Pubitemid 27149521)
77. Carelli, V. et al. Leber's hereditary optic neuroapathy (LHON) with 14484/ND6 mutation in a North African patient. J. Neurol. Sci. 160, 183-188 (1998). (Pubitemid 28522546)
78. Mashima, Y., Kigasawa, K., Wakakura, M. & Oguchi, Y. Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy? J. Neuroophthalmol. 20, 166-170 (2000).
79. Barnils, N., Mesa, E., Munoz, S., Ferrer-Artola, A. & Arruga, J. Response to idebenone and multivitamin therapy in Leber's hereditary optic neuropathy [Spanish]. Arch. Soc. Esp. Oftalmol. 82, 377-380 (2007).
80. Klopstock, K. et al. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain 134, 2677-2686 (2011).
81. Newman, N. J. Treatment of Leber hereditary optic neuropathy. Brain 134, 2447-2450 (2011).
82. Sadun, A. A. et al. Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy. Arch. Neurol. 69, 331-338 (2012).
83. DiMauro, S. & Mancuso, M. Mitochondrial diseases: therapeutic approaches. Biosci. Rep. 27, 125-137 (2007). (Pubitemid 46940941)
84. Koilkonda, R. D. & Guy, J. Leber's hereditary optic neuropathy-gene therapy: from benchtop to bedside. J. Ophthalmol. 2011, 179412 (2011).
85. Bouaita, A. et al. Downregulation of apoptosis-inducing factor in Harlequin mice induces progressive and severe optic atrophy which is durably prevented by AAV2-AIF1 gene therapy. Brain 135, 35-52 (2012).
86. Flierl, A. et al. Targeted delivery of DNA to the mitochondrial compartment via import sequence-conjugated peptide nucleic acid. Mol. Ther. 7, 550-557 (2003). (Pubitemid 36553425)
87. Guy, J. et al. Rescue of a mitochondrial deficiency causing Leber hereditary optic neuropathy. Ann. Neurol. 52, 534-4270 (2002).
88. Manfredi, G. et al. Rescue of an ATP synthesis deficiency in mtDNA-mutant human cells by transfer of MTATP6, a mtDNA-encoded gene, to the nucleus. Nat. Genet. 30, 394-399 (2002).
89. Bonnet, C. et al. Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or V subunits. Rejuvenation Res. 10, 127-144 (2007).
90. Marella, M., Seo, B. B., Thomas, B. B., Matsuno-Yagi, A. & Yagi, T. Successful amelioration of mitochondrial optic neuropathy using the yeast NDI1 gene in a rat animal model. PLoS ONE 5, e11472 (2010).
91. Guy, J. et al. Efficiency and safety of AAV mediated gene delivery of the human ND4 complex I subunit in the mouse visual system. Invest. Ophthalmol. Vis. Sci. 50, 4205-4214 (2009).
92. Qi, X., Sun, L., Lewin, A. S., Hauswirth, W. W. & Guy, J. The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse. Invest. Ophthalmol. Vis. Sci. 48, 1-10 (2007). (Pubitemid 47251378)
93. Ellouze, S. et al. Optimized allotropic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction. Am. J. Hum. Genet. 83, 373-387 (2008).
94. Floreani, M. et al. Antioxidant defences in cybrids harboring mtDNA mutations associated with Leber's hereditary optic neuropathy. FEBS J. 272, 1124-1135 (2005). (Pubitemid 40314932)
95. Qi, X. et al. Use of mitochondrial antioxidant defenses for rescue of cells with a Leber hereditary optic neuropathy-causing mutation. Arch. Ophthalmol. 125, 268-272 (2007).
96. Qi, X. et al. SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I. Ann. Neurol. 56, 182-191 (2004). (Pubitemid 39037914)
97. Yu, H. et al. Gene delivery to mitochondria by targeting modified adenoassociated virus suppresses Leber's hereditary optic neuropathy in a mouse model. Proc. Natl Acad. Sci. USA 109, E1238-E1247 (2012).
98. Tanaka, M. et al. Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria. J. Biomed. Sci. 9, 534-541 (2002). (Pubitemid 35316865)
99. Bacman, S. R. et al. Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a 'differential multiple cleavage-site' model. Gene Ther. 14, 1309-1318 (2007). (Pubitemid 47365618)
100. Chinnery, P. F., Andrews, R. M., Turnbull, D. M. & Howell, N. N. Leber hereditary optic neuropathy: does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation? Am. J. Med. Genet. 98, 235-243 (2001). (Pubitemid 32118987)
101. Tachibana, M. et al. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature 461, 367-372 (2009).
102. Craven, L. et al. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature 465, 82-85 (2010).
103. Lam, B. J. et al. Leber hereditary optic neuropathy gene therapy clinical trial recruitment: year 1. Arch. Ophthalmol. 128, 1129-1135 (2010).
104. Perales-Clemente, E. et al. Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal, undemonstrated mechanism or impossible task? Nucleic Acids Res. 39, 225-234 (2011).
105. Figueroa-Martinez, F. et al. What limits the allotropic expression of nucleus-encoded mitochondrial genes? The case of the chimeric Cox3 and Atp6 genes. Mitochondrion 11, 147-154 (2011).
106. Kyriakouli, D. S. et al. Progress and prospects: gene therapy for mitochondrial DNA disease. Gene Ther. 15, 1017-1023 (2008). (Pubitemid 351927692)
107. Stelmack, J. A. et al. Outcomes of the Veterans Affairs Low Vision Intervention Trial (LOVIT). Arch. Ophthalmol. 126, 608-617 (2008). (Pubitemid 351679554)
108. Kirkman, M. A. et al. Quality of life in patients with Leber hereditary optic neuropathy. Invest. Ophthalmol. Vis. Sci. 50, 3112-3115 (2009).
109. Kirkman, M. et al. Gene-environment interactions in Leber hereditary optic neuropathy. Brain 132, 2317-2326 (2009).
110. Newman, N. J. Leber hereditary optic neuropathy: bad habits, bad vision? Brain 132, 2306-2308 (2009).
111. Toomes, C. et al. Spectrum, frequency, and penetrance of OPA1 mutations in dominant optic atrophy. Hum. Mol. Genet. 10, 1369-1378 (2001). (Pubitemid 32640665)
112. Brown, D. T. et al. Transmission of mitochondrial DNA disorders: possibilities for the future. Lancet 368, 87-89 (2006).
113. Huoponen, K. et al. Genetic counseling in Leber hereditary optic neuropathy (LHON). Acta Ophthalmol. Scand. 80, 38-43 (2002). (Pubitemid 34506341)
114. Harding, A. E., Sweeney, M. G., Govan, G. G. & Riordan-Eva, P. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am. J. Hum. Genet. 57, 77-86 (1995).
115. Macmillan, C. et al. Pedigree analysis of French Canadian families with T14484C Leber's hereditary optic neuropathy. Neurology 50, 417-422 (1998).
116. Man, P. Y. et al. The epidemiology of Leber hereditary optic neuropathy in the North East of England. Am. J. Hum. Genet. 72, 339-339 (2003).
117. Nikoskelainen, E. K. Clinical picture of LHON. Clin. Neurosci. 2, 115-120 (1994).
118. Mackey, D. A. & Buttery, R. G. Leber hereditary optic neuropathy in Australia. Aust. N. Z. J. Ophthalmol. 20, 177-184 (1992). (Pubitemid 23197643)
119. Sadun, A. A. et al. Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy. Am. J. Ophthalmol. 136, 231-238 (2003). (Pubitemid 36904068)