Leber's hereditary optic neuropathy: A multifactorial disease

Progress in Retinal and Eye Research

Volumn 25, Issue 4, 2006, Pages 381-396

  Yen, May Yung ^a,b   Wang, An Guor ^a,b   Wei, Yau Huei ^b  

^a TAIPEI VETERANS GENERAL HOSPITAL   (Taiwan)

^b NATIONAL YANG MING UNIVERSITY   (Taiwan)

Author keywords

Complex I; Heteroplasmy; Leber's hereditary optic neuropathy; LHON; Mitochondria; Optic neuropathy

Indexed keywords

MITOCHONDRIAL DNA; PROTEIN SUBUNIT; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE; ROTENONE;

CELL DEATH; CHEMICAL ANALYSIS; CLINICAL FEATURE; DNA SEQUENCE; ENERGY YIELD; EPIGENETICS; GENE EXPRESSION; GENE LOCUS; GENE MUTATION; GENE THERAPY; HAPLOTYPE; HEREDITY; HETEROPLASMY; HUMAN; LEBER HEREDITARY OPTIC NEUROPATHY; LINKAGE ANALYSIS; MITOCHONDRIAL RESPIRATION; MUTATIONAL ANALYSIS; NONHUMAN; PRIORITY JOURNAL; PROGNOSIS; RETINA NERVE CELL; REVIEW; RISK ASSESSMENT; RISK FACTOR; TISSUE SPECIFICITY;

DNA, MITOCHONDRIAL; HUMANS; MUTATION; OPTIC ATROPHY, HEREDITARY, LEBER; PREVALENCE; PROGNOSIS; REACTIVE OXYGEN SPECIES; RISK FACTORS; SEX FACTORS;

EID: 33745870877     PISSN: 13509462     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.preteyeres.2006.05.002     Document Type: Review

References (146)

1. Andrews R.M., Griffiths P.G., Johnson M.A., and Turnbull D.M. Histochemical localization of mitochondrial enzyme activity in human optic nerve and retina. Br. J. Ophthalmol. 83 (1999) 231-235
2. Au H.C., Seo B.B., Matsuno-Yagi A., Yagi T., and Scheffler I.E. The NDUFA1 gene product (MWFE protein) is essential for activity of complex I in mammalian mitochondria. Proc. Natl. Acad. Sci. USA 96 (1999) 4354-4359
3. Bai Y., and Attardi G. The mtDNA-encoded ND6 subunit of mitochondrial NADH dehydrogenase is essential for the assembly of the membrane arm and the respiratory function of the enzyme. EMBO J. 17 (1998) 4848-4858
4. Baracca A., Solaini G., Sgarbi G., Lenza G., Baruzzi A., Schapira A.H.V., Martinuzzi A., and Carelli V. Severe impairment of complex I-driven adenosine triphosphate synthesis in Leber hereditary optic neuropathy cybrids. Arch. Neurol. 62 (2005) 730-736
5. 31P magnetic resonance spectroscopy in nonaffected carriers of 11778 mtDNA mutation. Neurology 45 (1995) 1364-1369
6. Barboni P., Savini G., Valentino M.L., Montagna P., Cortelli P., de Negri A.M., Sadun F., Bianchi S., Longanesi L., Zanini M., de Vivo A., and Carelli V. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy. Ophthalmology 112 (2005) 120-126
7. Barrientos A., and Moraes C.T. Titrating the effects of mitochondrial complex I impairment in the cell physiology. J. Biol. Chem. 274 (1999) 16188-16197
8. Barron M.J., Griffiths P., Turnbull D.M., Bates D., and Nichols P. The distributions of mitochondria and sodium channels reflect the specific energy requirements and conduction properties of the human optic nerve head. Br. J. Ophthalmol. 88 (2004) 286-290
9. Battisti C., Formichi P., Cardaioli E., Bianchi S., Maggiavacchi P., Tripodi S.A., Tosi P., and Federico A. Cell response to oxidative stress induced apoptosis in patients with Leber's hereditary optic neuropathy. J. Neurol. Neurosurg. Psychiatry 75 (2004) 1731-1736
10. Beretta S., Mattavelli L., Sala G., Tremolizzo L., Schapira A.H.V., Martinuzzi A., Carelli V., and Ferrarese C. Leber hereditary optic neuropathy mtDNA mutations disrupt glutamate transport in cybrid cell lines. Brain 127 (2004) 2183-2192
11. Besch D., Leo-Kottler B., Zrenner E., and Wissinger B. Leber's hereditary optic neuropathy: clinical and molecular genetic findings in a patient with a new mutation in the ND6 gene. Graefe's Arch. Clin. Exp. Ophthalmol. 237 (1999) 745-752
12. Black G.C., Morten K., Laborde A., and Poulton J. Leber's hereditary optic neuropathy: heteroplasmy is likely to be significant in the expression of LHON in families with the 3460 ND1 mutation. Br. J. Ophthalmol. 80 (1996) 91-97
13. Bristow E.A., Griffiths P.G., Andrews R.M., Johnson M.A., and Turnbull D.M. The distribution of mitochondrial activity in relation to optic nerve structure. Arch. Ophthalmol. 120 (2002) 791-796
14. Brown M.D., Torroni A., Reckord C.L., and Wallace D.C. Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations. Hum. Mutat. 6 (1995) 311-325
15. Brown M.D., Sun F., and Wallace D.C. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage. Am. J. Hum. Genet. 60 (1997) 381-387
16. Brown M.D., Trounce I.A., Jun A.S., Allen J.C., and Wallace D.C. Functional analysis of lymphoblast and cybrid mitochondria containing the 3460, 11778, or 14484 Leber hereditary optic neuropathy mitochondrial DNA mutation. J. Biol. Chem. 275 (2000) 39831-39836
17. Brown M.D., Zhadanov S., Allen J.C., Hosseini S., Newman N.J., Atamonov V.V., Mikhailovskaya I.E., Sukernik R.I., and Wallace D.C. Novel mtDNA mutations and oxidative phosphorylation dysfunction in Russian LHON families. Hum. Genet. 109 (2001) 33-39
18. Brown M.D., Allen J.C., Van Stavern G.P., Newman N.J., and Wallace D.C. Clinical, genetic, and biochemical characterization of a Leber hereditary optic neuropathy family containing both the 11778 and 14484 primary mutations. Am. J. Hum. Genet. 104 (2001) 331-338
19. Bu X., and Rotter J.I. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence on X-chromosome inactivation. Proc. Natl. Acad. Sci. USA 88 (1991) 8198-8202
20. Carelli V., Ghelli A., Bucchi L., Montagna P., De Negri A., Leuzzi V., Carducci C., Lenaz G., Lugaresi E., and Degri Esposti M. Biochemical features of mtDNA 14484 (ND6/M64 V) point mutation associated with Leber's hereditary optic neuropathy. Ann. Neurol. 45 (1999) 320-328
21. Carelli V., Napoli E., Valentino L., and Martinuzzi A. ROS production in cybrids carrying the three primary mutations associated with Leber's hereditary optic neuropathy. Neurology 58 Suppl. 3 (2002) A507
22. Carelli V., Vergani L., Bernazzi B., Zampieron C., Bucchi L., Valentino M.L., Rengo C., Torroni A., and Martinuzzi A. Respiratory function in cybrid cell lines carrying European mtDNA haplogroups : implications for Leber's hereditary optic neuropathy. Biochim. Biophys. Acta 1588 (2002) 7-14
23. Carelli V., Ross-Cisneros F.N., and Sadun A.A. Mitochondrial dysfunction as a cause of optic neuropathies. Prog. Retin. Eye Res. 23 (2004) 53-89
24. Carelli V., Rugolo M., Sgarbi G., Ghelli A., Zanna C., Baracca A., Lenaz G., Napoli E., Martinuzzi A., and Solaini G. Bioenergetics shapes cellular death pathways in Leber's hereditary optic neuropathy: a model of mitochondrial neurodegeneration. Biochim. Biophys. Acta 1658 (2004) 172-179
25. Carelli V., Achilli A., Valentino M.L., Rengo C., Semino O., Pala M., Olivieri A., Mattiazzi M., Pallotti F., Carrara F., Zeviani M., Leuzzi V., Carducci C., Valle G., Simionati B., Mendieta L., Salomao S., Belfort Jr. R., Sadun A.A., and Torroni A. Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber Hereditary Optic Neuropathy pedigrees. Am. J. Hum. Genet. 78 (2006) 564-574
26. Carroll J., Fearnley I.M., Shannon R.J., Hirst J., and Walker J.E. Analysis of the subunit composition of complex I from bovine heart mitochondria. Mol. Cell. Proteomics 2 (2003) 117-126
27. Chalmers R.M., and Harding A.E. A case-control study of Leber's hereditary optic neuropathy. Brain 119 (1996) 1481-1486
28. Chalmers R.M., Davis M.B., Sweeney M.G., Wood N.W., and Harding A.E. Evidence against and X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy. Am. J. Hum. Genet. 59 (1996) 103-108
29. Chinnery P.F., Howell N., Andrews R.M., and Turnbull D.M. Mitochondrial DNA analysis: polymorphisms and pathogenicity. J. Med. Genet. 36 (1999) 505-510
30. Chinnery P.F., Brown D.T., Andrews R.M., Singh-Kler R., Riordan-Eva P., Lindley J., Applegarth A.D., Turnbull D.M., and Howell N. The mitochondrial ND6 gene is a hot spot for mutations that cause Leber's hereditary optic neuropathy. Brain 124 (2001) 209-218
31. Chinnery P.F., Andrews R.M., Turnbull D.M., and Howell N. Leber hereditary optic neuropathy: does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation?. Am. J. Med. Genet. 98 (2001) 235-243
32. Chuman H., Nao-I N., Chuman T., Sawada A., Ozaki M., Futami Y., and Isashiki Y. Atypical Leber's hereditary optic neuropathy: a case with five different episodes of visual disturbance. Neuro-ophthalomology 22 (1999) 195-198
33. Cock H.R., Cooper J.M., and Schapira A.H.V. Functional consequences of the 3460-bp mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. J. Neurol. Sci. 165 (1999) 10-17
34. Danielson S.R., Wong A., Carelli V., Martinuzzi A., Schapira A.H.V., and Cortopassi G.A. Cells bearing mutations causing Leber's hereditary optic neuropathy are sensitized to Fas-induced apoptosis. J. Biol. Chem. 277 (2002) 5810-5815
35. Danielson S.R., Carelli V., Tan G., Martinuzzi A., Schapira A.H.V., Savontaus M.L., and Cortopassi G.A. Isolation of transcriptional changes attributable to LHON mutations and the cybridization process. Brain 128 (2005) 1026-1037
36. Degli Esposti M., Carelli V., Ghelli A., Ratta M., Crimi M., Sangiorgi S., Montagna P., Lenaz G., Lugaresi E., and Cortelli P. Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy. FEBS Lett. 352 (1994) 375-379
37. De Vries D.D., Went L.N., Bruyn G.W., Scholte H.R., Hofstra R.M.W., Bolhuis P.A., and van Oost B.A. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. Am. J. Hum. Genet. 58 (1996) 703-711
38. Erickson R.P. Leber's optic atrophy, a possible example of mitochondrial inheritance. Am. J. Hum. Genet. 24 (1972) 348-349
39. Fauser S., Luberichs J., Besch D., and Leo-Kottler B. Sequence analysis of the complete mitochondrial genome in patients with Leber's optic neuropathy lacking the three most common pathogenic DNA mutations. Biochem. Biophys. Res. Commun. 295 (2002) 342-347
40. Floreani M., Napoli E., Martinuzzi A., Pantano G., De Riva V., Trevisan R., Bisetto E., Valente L., Carelli V., and Dabbeni-Sala F. Antioxidant defences in cybrids harboring mtDNA mutations associated with Leber's hereditary optic neuropathy. FEBS J. 272 (2005) 1124-1135
41. Gajewski C.D., Yang L., Schon E.A., and Manfredi G. New insights into the bioenergetics of mitochondrial disorders using intracellular ATP reporters. Mol. Biol. Cell 14 (2003) 3628-3635
42. Ghelli A., Zanna C., Porcelli A.M., Schapira A.H.V., Martinuzzi A., Carelli V., and Rugolo M. Leber's hereditary optic neuropathy (LHON) pathogenic mutations induce mitochondrial-dependent apoptotic death in transmitochondrial cells incubated with galactose medium. J. Biol. Chem. 278 (2003) 4145-4150
43. Ghosh S.S., Fahy E., Bodis-Wollner I., Sherman J., and Howell N. Longitudinal study of a heteroplasmic 3460 Leber hereditary optic neuropathy family by multiplexed primary-extension analysis and nucleotide sequencing. Am. J. Hum. Genet. 58 (1996) 325-334
44. Guy J., Qi X., Pallotti F., Schon E.A., Manfredi G., Carelli V., Martinuzzi A., Hauswirth W.W., and Lewin A.S. Rescue of a mitochondrial deficiency causing Leber Hereditary optic neuropathy. Ann. Neurol. 52 (2002) 534-542
45. Handoko H.Y., Wirapati P.J., Sudoyo H.A., Sitepu M., and Marzuki S. Meiotic breakpoint mapping of a proposed X linked visual loss susceptibility locus in Leber's hereditary optic neuropathy. J. Med. Genet. 35 (1998) 668-671
46. Harding A.E., Sweeney M.G., Govan G.G., and Riordan-Eva P. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am. J. Hum. Genet. 57 (1995) 77-86
47. Herrnstadt C., Elson J.L., Fahy E., Preston G., Turnbull D.M., Anderson C., Ghosh S.S., Olefsky J.M., Beal M.F., Davis R.E., and Howell N. Reduced median network analysis of complete mtDNA coding region sequences for the major African, Asian, and European haplogroups. Am. J. Hum. Genet. 70 (2002) 1152-1170
48. Hofhaus G., Johns D.R., Hurko O., Attardi G., and Chomyn A. Respiration and growth defects in transmitochondrial cell lines carrying the 11778 mutation associated with Leber's hereditary optic neuropathy. J. Biol. Chem. 271 (1996) 13155-13161
49. Hollenbeck P.J. The pattern and mechanism of mitochondrial transport in axons. Front. Biosci. 1 (1996) d91-d102
50. Holt I.J., Miller D.H., and Harding A.E. Genetic heterogeneity and mitochondrial DNA heteroplasmy in Leber's hereditary optic neuropathy. J. Med. Genet. 26 (1989) 739-743
51. Howell N., and Mackey D.A. Low-penetrance branches in matrilineal pedigrees with Leber hereditary optic neuropathy. Am. J. Hum. Genet. 63 (1998) 1220-1224
52. Howell N., Bindoff A., McCullough D.A., Kubacka I., Poulton J., Mackey D., Taylor L., and Turnbull D.M. Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. Am. J. Hum. Genet. 49 (1991) 939-950
53. Howell N., Kubacka I., Xu M., and McCullough D.A. Leber hereditary optic neuropathy: involvement of the mitochondrial ND1 gene and evidence for an intragenic suppressor mutation. Am. J. Hum. Genet. 48 (1991) 935-942
54. Howell N., Xu M., Halvorson S., Bodis-Wollner I., and Sherman J. A heteroplasmic LHON family: tissue distribution and transmission of the 11778 mutation. Am. J. Hum. Genet. 55 (1994) 203-206
55. Howell N., Bogolin C., Jamieson R., Marenda D.R., and Mackey D.A. mtDNA mutations that cause optic neuropathy: how do we know?. Am. J. Hum. Genet. 62 (1998) 196-202
56. Howell N., Ghosh S.S., Fahy E., and Bindoff L.A. Longitudinal analysis of the segregation of mtDNA mutations in heteroplasmic individuals. J. Neurol. Sci. 172 (2000) 1-6
57. Howell N., Miller N.R., Mackey D.A., Arnold A., Herrnstadt C., Williams I.M., and Kubacka I. Lightening strikes twice: Leber hereditary optic neuropathy families with two pathogenic mtDNA mutations. J. Neuro-ophthalmol. 22 (2002) 262-269
58. Howell N., Oostra R., Bolhuis P.A., Spruijt L., Clarke L.A., Mackey D.A., Preston G., and Herrnstzdt C. Sequence analysis of the mitochondrial genomes from Dutch pedigrees with Leber hereditary optic neuropathy. Am. J. Hum. Genet. 72 (2003) 1460-1469
59. Howell N., Harrnstadt C., Shults C., and Mackey D.A. Low penetrance of the 14484 LHON mutation when it arises in a non-haplogroup J mtDNA background. Am. J. Med. Genet. 119A (2003) 147-151
60. Hudson G., Keers S., Man P.Y.W., Griffiths P., Huoponen K., Savontaus M.L., Nikoskelainen E., Zeviani M., Carrara F., Horvath R., Karcagi V., Spruijt L., de Coo I.F.M., Smeets H.J.M., and Chinnery P.F. Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. Am. J. Hum. Genet. 77 (2005) 1086-1091
61. Huoponen K., Villki J., Aula P., Nikoskelainen E.K., and Savontaus M.L. A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy. Am. J. Hum. Genet. 48 (1991) 1147-1153
62. Huoponen K., Lamminen T., Juvonen V., Aula P., Nikoskelainen E., and Savontaus M.L. The spectrum of mitochondrial DNA mutations in families with Leber hereditary optic neuroretinopathy. Hum. Genet. 92 (1993) 379-384
63. Isashiki T., Tabata Y., Kamimura K., and Ohba N. Genotypes of aldehyde dehydrogenase and alcohol dehydrogenase polymorphisms in patients with Leber's hereditary optic neuropathy. Jpn. J. Hum. Genet. 42 (1997) 187-191
64. Ishikawa K., Funayama T., Ohde H., Inagaki Y., and Mashima Y. Genetic variants of TP53 and EPHX1 in Leber's hereditary optic neuropathy and their relationship at age at onset. Jpn. J. Ophthalmol. 49 (2005) 121-126
65. Jacobi F.K., Leo-Kottler B., Mittelviefbaus K., Zrenner E., Meyer J., Puscb C.M., and Wissinger B. Segregation patterns and heteroplasmy prevalence in Leber's hereditary optic neuropathy. Invest. Ophthalmol. Vis. Sci. 42 (2001) 1208-1214
66. Johns D.R., Neufeld M.J., and Park R.D. An ND6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. Biochem. Biophys. Res. Commun. 187 (1992) 1551-1557
67. Jun A.S., Brown M.D., and Wallace D.C. A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrigenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia. Proc. Natl. Acad. Sci. USA 91 (1994) 6206-6210
68. Juvonen V., Nikoskelainen E., Lamminen T., Penttinen M., Aula P., and Savontaus M.L. Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with Leber hereditary optic neuropathy. Hum. Mut. 9 (1997) 412-417
69. Kaplanova V., Zeman J., Hansikova H., Cerna L., Houst'kova H., Misovicova N., and Houstek J. Segregation pattern and biochemical effect of the G3460A mtDNA mutation in 27 members of LHON family. J. Neurol. Sci. 223 (2004) 149-155
70. Kerrison J.B. Latent, acute, and chronic Leber's hereditary optic neuropathy. Ophthalmology 112 (2005) 1-2
71. Kerrison J.B., Miller N.R., Hsu F.C., Beaty T.H., Maumenee I.H., Smith K.H., Savino P.J., Stone E.M., and Newman N.J. A case-control study of tobacco and alcohol consumption in Leber hereditary optic neuropathy. Am. J. Ophthalmol. 130 (2000) 803-812
72. Kim J.Y., Hwang J.M., and Park S.S. Mitochondrial DNA C4171A/ND1 is a novel primary causative mutation of Leber's hereditary optic neuropathy with a good prognosis. Ann. Neurol. 51 (2002) 630-634
73. King M.P., and Attardi G. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246 (1989) 500-503
74. Klivenyi P., Karg E., Rozsa C., Horvath R., Komoly S., Nemeth I., Turi S., and Vecsei L. α-Tocopherol/lipid ratio in blood is decreased in patients with Leber's hereditary optic neuropathy and asymptomatic carriers of the 11778 mtDNA mutation. J. Neurol. Neyrosurg. Psychiatry 70 (2001) 359-362
75. Kudin A.P., Bimpong-Buta N.Y., Vielhaber S., Elger C.E., and Kunz W.S. Characterization of superoxide-producing sites in isolated brain mitochondria. J. Biol. Chem. 279 (2004) 4127-4135
76. Lagerstrom-Fermer M., Olsson C., Forsgren L., and Syvanen A.C. Heteroplsmy of human mtDNA control region remains constant during life. Am. J. Hum. Genet. 68 (2001) 1299-1301
77. Lamminen T., Huoponen K., Sistonen P., Juvonen V., Lahermo P., Aula P., Nikoskelainen E., and Savontaus M.L. mtDNA haplotype analysis in Finnish families with Leber hereditary optic neuropathy. Eur. J. Hum. Genet. 5 (1997) 171-279
78. Leber T. Ueber hereditare und congenital-angelegte Sehnerven-leiden. Graefe's Arch. Ophthalmol. 17 (1871) 249-291
79. 31P magnetic resonance spectroscopy. Ann. Neurol. 42 (1997) 573-579
80. Lodi R., Montagna P., Cortelli P., Iotti S., Cevoli S., Carelli V., and Barbiroli B. "Secondaty" 4216/ND1 and 13708/ND5 Leber's hereditary optic neuropathy mitochondrial DNA mutations do not further impair in vivo mitochondrial oxidative metabolism when associated with the 11778/ND4 mitochondrial DNA mutation. Brain 123 (2000) 1896-1902
81. Mackey D., and Howell N. A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology. Am. J. Hum. Genet. 51 (1992) 1218-1228
82. Mackey D.A., Oostra R.J., Rosenberg T., Nikoskelainen E., Bronte-Stewart J., Poulton J., Harding A.E., Govan G., Bolhuis P.A., and Norby S. Primary pathologic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. Am. J. Hum. Genet. 59 (1996) 481-485
83. Majander A., Finel M., Savontaus M.L., Nikoskelainen E., and Wikstrom M. Catalytic activity of complex I in cell lines that possess replacement mutations in the ND genes in Leber's hereditary optic neuropathy. Eur. J. Biochem. 239 (1996) 201-207
84. Man P.Y.W., Brown D.T., Wehnert M.S., Zeviani M., Carrara F., Turnbull D.M., and Chinnery P.F. NDUFA-1 is not a nuclear modifier gene in Leber's hereditary optic neuropathy. Neurology 58 (2002) 1861-1862
85. Man P.Y.W., Griffiths P.G., Brown N., Howell D.M., Turnbull D.M., and Chinnery P.F. The epidemiolgy of Leber hereditary optic neuropathy in the North East of England. Am. J. Hum. Genet. 72 (2003) 333-339
86. Man P.Y.W., Howell N., Mackey D.A., Norby S., Rosenberg T., Trunbull D.M., and Chinnery P.F. Mitochondrial DNA haplogroup distribution within Leber hereditary optic neuropathy pedigrees. J. Med. Genet. 41 (2004) e41
87. Man C.Y.Y.W., Chinnery P.F., and Griffiths P.G. Optic neuropathies-importance of spatial distribution of mitochondria. Med. Hypotheses 65 (2005) 1038-1042
88. Mashima Y., Yamada K., Wakakura M., et al. Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neuropathy. Curr. Eye Res. 17 (1998) 403-408
89. Mashima Y., Sato E.A., Ohde H., and Oguchi Y. Macular nerve fibers temporal to fovea may have a greater potential to recovery function in patients with Leber's hereditary optic neuropathy. Jpn. J. Ophthalmol. 46 (2002) 660-667
90. Matthews P.M., Brown R.M., Morten K., Marchington D., Poulton J., and Brown G. Intracellular heteroplasmy for disease-associated point mutations in mtDNA: implications for disease expression and evidence for mitotic segregation of heteroplasmic units of mtDNA. Hum. Genet. 96 (1995) 261-268
91. Nakamura N., Fujiwara Y., and Yamamoto M. The two locus control of Leber hereditary optic neuropathy and a high penetrance in Japanese pedigrees. Hum. Genet. 91 (1993) 339-341
92. Newman N.J. Leber's hereditary optic neuropathy: new genetic consideration. Arch. Neurol. 50 (1993) 540-548
93. Newman N.J. Hereditary optic neuropathies. In: Miller N.R., and Newman N.J. (Eds). Walsh & Hoyt's Clinical Neuro-Ophthalmology (2005), Lippincott Williams & Wilkins, Philadelphia 466-476
94. Newman N.J., Lott M.T., and Wallace D.C. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am. J. Ophthalmol. 111 (1991) 750-762
95. Newman-Toker D.E., and Horton J.C. Recurrent visual loss in Leber hereditary optic neuropathy. Arch. Ophthalmol. 121 (2003) 288-291
96. Nikoskelainen E.K., Hoyt W.F., and Nummelin K. Ophthalmoscopic findings in Leber's hereditary optic neuropathy, II: the fundus findings in the affected family member's. Arch. Ophthalmol. 101 (1983) 1059-1068
97. Ochs S., and Hollingsworth D. Dependence of fast axoplasmic transport in nerve on oxidative metabolism. J. Neurochem. 18 (1971) 107-114
98. Oostra R.J., Bolhuis P.A., Wijburg F.A., Zorn-Ende G., and Bleeker-Wagemakers E.M. Leber's hereditary optic neuropathy: correlation between mitochondrial genotype and visual outcome. J. Med. Genet. 31 (1994) 280-286
99. Oostra R.J., Bolhuis P.A., Zorn-Ende I., de Kok-Nazaruk M.M., and Bleeker-Wagemakers E.M. Leber's hereditary optic neuropathy: no significant evidence for primary or secondary pathogenicity of the 15257 mutation. Hum. Genet. 94 (1994) 256-270
100. Oostra R.J., Kemp S., Bolhuis P.A., and Bleeker-Wagemakers E.M. No evidence for "skewed" inactivation of the X-chromosome as cause of Leber's hereditary optic neuropathy in female carriers. Hum. Genet. 87 (1996) 500-505
101. Ortiz R.G., Newman N.J., Manoukian S.V., Diesenhouse M.C., Lott M.T., and Wallace D.C. Optic disc cupping and electrocardiographic abnormalities in an American pedigree with Leber's hereditary optic neuropathy. Am. J. Ophthalmol. 113 (1992) 561-566
102. Pegoraro E., Carelli V., Zeviani M., Cortelli P., Montagna P., Barboni P., Angelini C., and Hoffman E.P. X-inactivation patterns in female Leber's hereditary optic neuropathy patients do not support a strong X-linked determinant. Am. J. Med. Genet. 61 (1996) 356-362
103. Pegoraro E., Vettori A., Valentino M.L., Molon A., Mostacchiuolo M.L., Howell N., and Carelli V. X-inactivation pattern in multiple tissues from two Leber's hereditary optic neuropathy (LHON) patients. Am. J. Med. Genet. 119A (2003) 37-40
104. Pezzi P.P., de Negri A.M., Sadun F., Carelli V., and Leuzzi V. Childhood Leber's hereditary optic neuropathy (ND1/3460) with visual recovery. Pediatr. Neurol. 19 (1998) 308-312
105. Pitkanen S., and Robinson B.H. Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase. J. Clin. Invest. 98 (1996) 345-351
106. Puomila A., Viitanen T., Savontaus M.L., Nikoskelainen E., and Huoponen K. Segregation of the ND4/11778 and the ND1/3460 mutations in four heteroplasmic LHON families. J. Neurol. Sci. 205 (2002) 41-45
107. Qi X., Lewin A.S., Hauswirth W.W., and Guy J. Suppression of complex I gene expression induces optic neuropathy. Ann. Neurol. 53 (2003) 198-205
108. Qi X., Lewin A.S., Hauswirth W.W., and Guy J. Optic neuropathy induced by reduction in mitochondrial superoxide dismutase. Invest. Ophthalmol. Vis. Sci. 44 (2003) 1088-1096
109. Raha S., and Robinson B.H. Mitochondria, oxygen free radicals, and apoptosis. Am. J. Med. Genet. 106 (2001) 62-70
110. Riordan-Eva P., Sanders M.D., Govan G.G., Sweeney M.G., Costa J.D., and Harding A.E. The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain 118 (1995) 319-337
111. Robinson B.H. Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect. Biochim. Biophys. Acta 1364 (1998) 271-286
112. Saadati H.G., Hsu H.Y., Heller K.B., and Sadun A.A. A histopathologic and morphometric differentiation of nerves in optic nerve hypoplasia and Leber hereditary optic neuropathy. Arch. Ophthalmol. 116 (1998) 911-916
113. Sabri M.I., and Ochs S. Relationship of ATP and creatine phosphate to fast axoplasmic transport in mammalian nerve. J. Neurochem. 19 (1972) 2821-2828
114. Sadun A.A., Kashima Y., Wurdeman A.E., Dao J., Heller K., and Sherman J. Morphological findings in the visual system in a case of Leber's hereditary optic neuropathy. Clin. Neurosci. 2 (1994) 165-172
115. Sadun A.A., Win P.H., Ross-Cisneros F.N., Walker S.O., and Carelli V. Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve. Trans. Am. Ophthalmol. Soc. 98 (2000) 223-232
116. Sadun A.A., Carelli V., Salomao S.R., Berezovsky A., Quiros P., Sadun F., DeNegri A.M., Andrade R., Schein S., and Belfort R. A very large Brazilian pedigree with 11778 Leber's hereditary optic neuropathy. Trans. Am. Ophthalmol. Soc. 100 (2002) 169-180
117. Sadun A.A., Carelli V., Salomao S.R., Berezovsky A., Quiros P.A., Sadun F., DeNegri A.M., Andrade R., Moraes M., Passos A., Kjaer P., Pereira J., Valentino M.L., Schein S., and Belfort R. Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy. Am. J. Ophthalmol. 136 (2003) 231-238
118. Savini G., Barboni P., Valentino M.L., Montagna P., Cortelli P., De Negri A.M., Sadun F., Bianchi S., Longanesi L., Zanini M., and Carelli V. Retinal nerve fiber layer evaluation by optical coherence tomography in unaffected carriers with Leber's hereditary optic neuropathy mutations. Ophthalmology 112 (2005) 127-131
119. Shankar S.P., Carelli V., King T.M., Taylor C.M., Abdulkawy H., Braun T.A., Daiger S.P., Alomao S.R., Sadun A.A., and Stone E.M. Linkage analysis of the X chromosome in a Brazilian family with leber hereditary optic neuropathy (LHON). Invest. Ophthalmol. Vis. Sci. 46 (2005) (E-abstract 663)
120. Siregar N.C., Jean-Francois M.J., Blok R.B., and Byrne E. Genotype and phonotype changes in exhaustively grown cell lines from mitochondrial cytopathy patients. Muscle Nerve 21 (1998) 599-609
121. Smith J.L., Hoyt W.F., and Susac J.O. Ocular fundus in acute Leber optic neuropathy. Arch. Ophthalmol. 90 (1973) 349-354
122. Smith K.H., John D.R., Heher K.L., and Miller N.R. Heteroplasmy in Leber's hereditary optic neuropathy. Arch. Ophthalmol. 111 (1993) 1486-1490
123. Stone E.M., Newman N.J., Miller N.R., Johns D.R., Lott M.T., and Wallace D.C. Visual recovery in patients with Leber's hereditary optic neuropathy and the 11778 mutation. J. Clin. Neuroophthalmol. 12 (1992) 10-14
124. Sweeney M.G., Davis M.B., Lashwood A., Brockington M., Toscano A., and Harding A.E. Evidence against and X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy. Am. J. Hum. Genet. 51 (1992) 741-748
125. Taso K., Aitken P.A., and Johns D.R. Smoking as an aetiological factor in a pedigree with Leber's hereditary optic neuropathy. Br. J. Ophthalmol. 83 (1999) 577-581
126. Torroni A., Petrozzi M., D'Urbano L., Sellitto D., Zeviani M., Carrara F., Carducci C., Leuzzi V., Carelli V., Barboni P., De Negri A., and Scozzari R. Haplotype and phylogenic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484. Am. J. Hum. Genet. 60 (1997) 1107-1121
127. Valentino M.L., Barboni P., Ghelli A., Bucchi L., Rengo C., Achilli A., Torroni A., Lugaresi A., Lodi R., Barbiroli B., Dotti M.T., Federico A., Baruzzi A., and Carelli V. The ND1 gene of complex I is a mutational hot spot for Leber's hereditary optic neuropathy. Ann. Neurol. 56 (2004) 631-641
128. Vergani L., Martinuzzi A., Carelli V., Cortelli P., Montagna P., Schievano G., Carrozzo R., Angelini C., and Lugaresi E. mtDNA mutations associated with Leber's hereditary optic neuropathy: studies on cytoplasmic hybrid (cybrid) cells. Biochem. Biophys. Res. Commun. 210 (1995) 880-888
129. Wallace D.C., Singh G., Lott M.T., Hodge J.A., Schurr T.G., Lezza A.M., Elsas L.J., and Nikoskelainen E.K. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 242 (1998) 1427-1430
130. Wallace D.C., Brown M.D., and Lott M.T. Mitochondrial DNA variation in human evolution and disease. Gene 238 (1999) 211-230
131. Wang L., Dong J., Cull G., Fortune B., and Cioffi G.A. Varicosities of intraretinal ganglion cell axons in human and nonhuman primates. Invest. Ophthalmol. Vis. Sci. 44 (2003) 2-9
132. Weiss M.M., Hermsen M.A., Meijer G.A., van Grieken N.C., Baak J.P., Kuipers E.J., and van Diest P.J. Comparative genomic hybridization. Mol. Pathol. 52 (1999) 243-251
133. Wissinger B., Besch D., Baumann B., Fauser S., Christ-Alder M., Jurklies B., Zrenner E., and Leo-Kottler B. Mutation analysis of the ND6 gene in patients with Lebers hereditary optic neuropathy. Biochem. Biophys. Res. Commun. 234 (1997) 511-515
134. Wong A., and Cortopassi G. mtDNA mutations confer cellular sensitivity to oxidant stress that is partially rescued by calcium depletion and cyclosporin A. Biochem. Biophys. Res. Commun. 239 (1997) 139-145
135. Wong A., Cavelier L., Collins-Schramm H.E., Seldin M.F., McGrogan M., Savontaus M.L., and Cortopassi G.A. Differentiation-specific effects of LHON mutations introduced into neuronal NT2 cells. Hum. Mol. Genet. 11 (2002) 431-438
136. Yen M.Y., Lee H.C., Liu J.H., and Wei Y.H. Compensatory elevation of complex II activity in Leber's hereditary optic neuropathy. Br. J. Ophthalmol. 80 (1996) 78-81
137. Yen M.Y., Lee J.F., Liu J.H., and Wei Y.H. Eneygy charge is not decreased in lymphocytes of patients with Leber's hereditary optic neuropathy with the 11778 mutation. J. Neuro-Ophthalmol. 18 (1998) 84-85
138. Yen M.Y., Wang A.G., Chang W.L., Hsu W.M., Liu J.H., and Wei Y.H. Leber's hereditary optic neuropathy-the spectrum of mitochondrial DNA mutations in Chinese patients. Jpn. J. Ophthalmol. 46 (2002) 45-51
139. Yen M.Y., Chen C.S., Wang A.G., and Wei Y.H. Increase of mitochondrial DNA in blood cells of patients with Leber's hereditary optic neuropathy with 11778 mutation. Br. J. Ophthalmol. 86 (2002) 1027-1030
140. Yen M.Y., Chen Y.J., Lin C.H., Wang A.G., and Wei Y.H. Genetic analysis in Leber's hereditary optic neuropathy using the comparative genomic hybridization technique. Clin. Exp. Ophthalmol. 31 (2003) 435-438
141. Yen M.Y., Kao S.H., Wang A.G., and Wei Y.H. Increased 8-hydroxy-2′-deoxyguanosine in leukocyte DNA in Leber's hereditary optic neuropathy. Invest. Ophthalmol. Vis. Sci. 45 (2004) 1688-1691
142. Zanna C., Ghelli A., Forcelli A.M., Carelli V., Martinuzzi A., and Rugolo M. Apoptotic cell death of cybrids bearing LHON mutations is caspase-independent. Ann. N.Y. Acad. Sci. 1010 (2003) 213-217
143. Zanna C., Ghelli A., Porcelli A.M., Martinuzzi A., Carelli V., and Rugolo M. Caspase-independent death of Leber's hereditary optic neuropathy cybrids is driven by energetic failure and mediated by AIF and endonuclease G. Apoptosis 10 (2005) 997-1007
144. Zhang X., Jones D., and Gonzalez-Lima F. Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction. Neurosci. Lett. 326 (2002) 97-100
145. Zhadanov S.I., Atamanov V.V., Zhadanov N.I., Oleinikov O.V., Osipova L.P., and Schurr T.G. A novel mtDNA ND6 gene mutation associated with LHON in a Caucasian family. Biochem. Biophys. Res. Commun. 332 (2005) 1115-1121
146. Zhuchenko O., Wehnert M., Bailey J., Sun Z.S., and Lee C.C. Isolation, mapping, and genomic structure of an X-linked gene for a subunit of human mitochondrial complex I. Genomics 37 (1996) 281-288