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A review of primary hereditary optic neuropathies

  • Published:
Journal of Inherited Metabolic Disease

Abstract

Summary: The primary inherited optic neuropathies are a heterogeneous group of disorders that result in loss of retinal ganglion cells, leading to the clinical appearance of optic atrophy. They affect between 1:10 000 to 1:50 000 people. The main clinical features are a reduction in visual acuity, colour vision abnormalities, centro-caecal visual field defects and pallor of the optic nerve head. Electrophysiological testing shows a normal flash electroretinogram, absentor delayed pattern visually evoked potentials suggestive of a conduction deficit and N95 waveform reduction on the pattern electroretinogram, consistent with a primary ganglion cell pathology. The primary inherited optic neuropathies may be sporadic or familial. The mode of inheritance may be autosomal dominant, autosomal recessive, X-linked recessive or mitochondrial. Within each of these groups, the phenotypic characteristics vary in such features as the mode and age of onset, the severity of the visual loss, the colour deficit and the overall prognosis. A number of different genes (most as yet unidentified) in both nuclear and mitochondrial genomes, underlie these disorders. The elucidation of the role of the encoded proteins will improve our understanding of basic mechanisms of ganglion cell development, physiology and metabolism and further our understanding of the pathophysiology of optic nerve disease. It will also improve diagnosis, counselling and management of patients, and eventually lead to the development of new therapeutic modalities.

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REFERENCES

  • Alexander C, Votruba M, Pesch U, et al (2000) OPAl, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nature Genetics 26: 211-215.

    PubMed  CAS  Google Scholar 

  • Anikster Y, Kleta R, Shaag A, Gahl WA, Elpeleg O (2001) Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews. Am J Hum Genet 69: 1218-1224.

    PubMed  CAS  Google Scholar 

  • Assink JJM, Tijmes NT, tenBrink JB, et al (1997) A gene for X-linked optic atrophy is closely linked to the Xpl 1.4Xpl 1.2 region of the X chromosome. Am J Hum Genet 61: 934-939.

    PubMed  CAS  Google Scholar 

  • Aung T, Ocaka L, Ebeneezer N, et al (2002a) A major marker for normal tension glaucoma: association with polymorphisms in the OPAl gene. Hum Genet 110: 52-56.

    PubMed  CAS  Google Scholar 

  • Aung T, Ocaka L, Ebenezer ND, et al (2002b) Investigating the association between OPAl polymorphisms and glaucoma: comparison between normal tension and high tension primary open angle glaucoma. Hum Genet 110: 513-514.

    PubMed  CAS  Google Scholar 

  • Batten B (1896) A family suffering from hereditary optic atrophy. Trans Ophthalmol Soc UK 16: 125.

    Google Scholar 

  • Berninger TA, Jaeger W, Krastel H (1991) Electrophysiology and colour perimetry in dominant infantile optic atrophy. Br J Ophthalmol 75: 49-52.

    PubMed  CAS  Google Scholar 

  • Bristow EA, Griffiths PG, Andrews RM, Johnson MA, Turnbull DM (2002) The distribution of mitochondrial activity in relation to optic nerve structure. Arch Ophthalmol 120: 791-796.

    PubMed  Google Scholar 

  • Bu X, Rotter JI (1991) X-chromosome linked and mitochondrial gene control of Leber's here-ditary optic neuropathy: evidence from segregation analysis for dependence on X chromo-some inactivation. Proc Natl Acad Sci USA 88: 8198-8202.

    PubMed  CAS  Google Scholar 

  • Carelli V, Ross-Cisneros FN, Sadun AA (2002) Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies. Neurochem Int 40: 673-684.

    Google Scholar 

  • Carroll WM, Mastaglia FL (1979) Leber's optic neuropathy; a clinical and evoked potential study of a six generation family. Brain 102: 559-580.

    PubMed  CAS  Google Scholar 

  • Chen J-D, Denton MJ (1991) X-chromosomal gene in Leber hereditary optic neuroretinopathy (Letter). Am J Hum Genet 48: 692-693.

    Google Scholar 

  • Chen J-D, Cox I, Denton MJ (1989) Preliminary eclusion of an X-linked gene in Leber optic atrophy by linkage analysis. Hum Genet 82: 203-207.

    PubMed  CAS  Google Scholar 

  • Cordes FC (1952) Optic atrophy in infancy, childhood and adolescence. Am J Ophthalmol 35: 1272-1284.

    PubMed  CAS  Google Scholar 

  • Delettre C, Lenaers G, Griffoin J, et al (2000) Nuclear gene OPAl, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nature Genet 26: 207-210.

    PubMed  CAS  Google Scholar 

  • Delettre C, Griffoin J-M, Kaplan J, et al (2001) Mutation spectrum and splicing variants in the OPAl gene. Hum Genet 109: 584-591.

    PubMed  CAS  Google Scholar 

  • Eiberg H, Kjer B, Kjer P, Rosenberg T (1994) Dominant optic atrophy (OPAl) mapped to chromosome 3q region. I. Linkage analysis. Hum Mol Genet 3: 977-980.

    PubMed  CAS  Google Scholar 

  • Eliott MD, Traboulsi EI, Maumenee IH (1993) Visual prognosis in autosomal dominant optic atrophy (Kjer type). Am J Ophthalmol 115: 360-367.

    PubMed  CAS  Google Scholar 

  • Fingert JH, Heon E, Liemann JM, et al (1999) Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. Hum Mol Genet 8: 899-905.

    PubMed  CAS  Google Scholar 

  • Fingert JH, Affatigato LM, Secrist JL, Shanker SP, Sheffield VC, Stone EM (2002) Identifi-cation of a novel OPAl mutation in a large family with severe dominant optic atrophy phenotype. Invest Ophthalmol Vis Sci 43: E-Abstract 2397.

    Google Scholar 

  • Flanigan KM, Johns DR (1993) Association of the 11778 mitochondrial DNA mutation and demyelinating disease. Neurol 43: 2720-2722.

    CAS  Google Scholar 

  • Foroozan R, Buono LM, Sergott RC, Savino PJ (2002) Is normal tension glaucoma actually an unrecognized hereditary optic neuropathy? New evidence from genetic analysis. Curr Opin Ophthalmol 13: 362-370.

    PubMed  Google Scholar 

  • Fournier AV, Damj KF, Epstein DL, Pollock SC (2001) Disc excavation in dominant optic atrophy: differentiation from normal tension glaucoma. Ophthalmol 108: 1595-1602.

    CAS  Google Scholar 

  • Gass A, Barker GJ, MacManus D, et al (1995) High resolution magnetic resonance imaging of the anterior visual pathway in patients with optic neuropathies using fast spin echo and phased array local coils. J Neurol Neurosurg Psychiatry 58: 562-569.

    PubMed  CAS  Google Scholar 

  • Giles RE, Blanc H, Cann HM, Wallace DC (1980) Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci USA 77: 6715-6719.

    PubMed  CAS  Google Scholar 

  • Gyllensten U, Wharton D, Josefson A, Warton AC (1991) Paternal inheritance of mitochondrial DNA in mice. Nature 352: 255-257.

    PubMed  CAS  Google Scholar 

  • Halpern DL, Grosskreutz CL (2002) Glaucomatous optic neuropathy: mechanisms of disease. Ophthalmol Clin N Am 15: 61-68.

    Google Scholar 

  • Harding A, Sweeney MG, Govan GG, Riordan-Eva P (1995) Pedigree analysis in Leber here-ditary optic neuropathy families with a pathogenic mtDNA mutation. Am J Hum Genet 57: 77-86.

    PubMed  CAS  Google Scholar 

  • Harding AE, Sweeney MG, Miller DH, Mumford CJ, Kellar-Wood, Hal DMe (1992) Occur-rence of a multiple sclerosis-like illness in women who have a Leber's hereditary optic neuropathy mitochondrial DNA mutation. Brain 115: 979-989.

    PubMed  Google Scholar 

  • Heher KL, Johns DR (1993) Maculopathy associated with the 15257 mitochondrial DNA mutation. Arch Ophthalmol 111: 1495-1499.

    PubMed  CAS  Google Scholar 

  • Holder GE (1991) The incidence of abnormal pattern electroretinography in optic nerve demyelination. Electroencephalogr Clin Neurophysiol 78: 18-26.

    PubMed  CAS  Google Scholar 

  • Holder GE, Votruba M, Carter AC, Bhattacharya SS, Fitzke FW, Moore AT (1998) Electro-physiological findings in dominant optic atrophy (DOA) linking to the OPAl locus on chromosome 3q 28-qter. Doc Ophthalmol 95: 217-228.

    PubMed  Google Scholar 

  • Howell N, Bindoff LA, McCullough DA, et al (1991a) Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. Am J Hum Genet 49: 939-950.

    PubMed  CAS  Google Scholar 

  • Howell N, Halvorsen S, Burns J, McCullough DA, Paulton J (1993) When does bilateral optic atrophy become Leber hereditary optic neuropathy? Am J Hum Genet 53: 959-963.

    PubMed  CAS  Google Scholar 

  • Howell N, Xu M, Halvorson S, Bodis-Wollner I, Sherman J (1994) A heteroplasmic LHON family: tissue distribution and transmission of the 11778 mutation. Am J Hum Genet 55: 203-206.

    PubMed  CAS  Google Scholar 

  • Howell N, Kubacka I, Halvorson S, Howell B, McCullough DA, Mackey D (1995) Phylogenetic analysis of the mitochondrial genomes from Leber hereditary optic neuropathy pedigrees. Genetics 140: 285-302.

    PubMed  CAS  Google Scholar 

  • Hoyt CS (1980) Autosomal dominant optic atrophy: a spectrum of disability. Ophthalmology 87: 245-251.

    PubMed  CAS  Google Scholar 

  • Huoponen K, Lamminen T, Juvonen V, Aula P, Nikoskelainen E, Savontaus ML (1993) The spectrum of mitochondrial DNA mutations in families with Leber hereditary optic neuroretinopathy. Hum Genet 92: 379-384.

    PubMed  CAS  Google Scholar 

  • Jeager W, Fruh D, Lauer HJ (1972) Types of acquired colour deficiencies caused by autosomal-dominant infantile optic atrophy. Acquired colour vision deficiencies. In Verriest G., ed. Modern Problems in Ophthalmology. Basel: Karger, 145-147.

    Google Scholar 

  • Johns DR, Neufeld MJ (1991) Cytochrome b mutations in Leber hereditary optic neuropathy. Biochem Biophys Res Commun 181: 1358-1364.

    PubMed  CAS  Google Scholar 

  • Johns DR, Neufeld MJ (1993) Cytochrome c oxidase mutations in Leber hereditary optic neuropathy. Biochem Biophys Res Commun 196: 810-815.

    PubMed  CAS  Google Scholar 

  • Johns DR, Neufeld MJ, Park RD (1992) An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. Biochem Biophys Res Commun 187: 1551-1557.

    PubMed  CAS  Google Scholar 

  • Johns DR, Heher KL, Miller NR, Smith KH (1993) Leber's hereditary optic neuropathy Clini-cal manifestations of the 14484 mutation. Arch Ophthalmol 111: 495-498.

    PubMed  CAS  Google Scholar 

  • Johnston PB, Gaster RN, Smith VC, Tripathi RC (1979) A clinicopathological study of autosomal dominant optic atrophy. Am J Ophthalmol 88: 868-875.

    PubMed  CAS  Google Scholar 

  • Jonasdottir A, Eiberg H, Kjer B, Kjer P, Rosenberg T (1997) Refinement of the dominant optic atrophy locus (OPAl) to a 1.4-cM interval on chromosome 3q28-3q29, within a 3-Mb YAC contig. Hum Genet 99: 115-120.

    PubMed  CAS  Google Scholar 

  • Jun AS, Brown MD, Wallace DC (1994) A mitochondrial DNA mutation at np14459 of the ND6 gene associated with maternally inherited Leber's hereditary optic neuropathy and dystonia. Proc Natl Acad Sci USA, 91: 6206-6210.

    PubMed  CAS  Google Scholar 

  • Juvonen V, Vilkki J, Aula P, Nikoskelainen E, Savontaus ML (1993) Reevaluation of the linkage of an optic atrophy susceptibility gene to X-chromosomal markers in Finnish families with Leber hereditary optic neuropathy (LHON). Am J Hum Genet 53: 289-292.

    PubMed  CAS  Google Scholar 

  • Kamal D, Hitchings R (1998) Normal tension glaucoma a practical approach. Br J Ophthalmol 82: 835-840.

    PubMed  CAS  Google Scholar 

  • Kellar-Wood H, Robertson N, Govan GG, Compston DAS, Harding AE (1994) Leber's here-ditary optic neuropathy mitochondrial DNA mutations in multiple sclerosis. Ann Neurol 36: 109-112.

    PubMed  CAS  Google Scholar 

  • Kermode AG, Moseley IF, Kendal BE, Miller DH, Macmanus DG, McDonald WI (1989) Magnetic resonance imaging in Leber's optic neuropathy. J Neurol Neurosurg Pscyhiatry 52: 671-674.

    CAS  Google Scholar 

  • Kerrison JB, Howell N, Miller NR, Hirst L, Green WR (1995) Leber hereditary optic neuropathy. Electron microscopy and molecular genetic analysis of a case. Ophthalmology 102: 1509-1516.

    PubMed  CAS  Google Scholar 

  • Kivlin JD, Lovrien EW, Bishop DT, Maumenee IH (1983) Linkage analysis in dominant optic atrophy. Am J Hum Genet 35: 1190-1195.

    PubMed  CAS  Google Scholar 

  • Kjer P (1959) Infantile optic atrophy with dominant mode of inheritance: a clinical and genetic study of 19 Danish families. Acta Ophthalmol Scand 37 (supplement 54 ):1-146.

    Google Scholar 

  • Kjer P (1983) Histopathology of eye, optic nerve and brain in a case of dominant optic atrophy. Acta Ophthalmol Scand 61: 300-312.

    CAS  Google Scholar 

  • Kjer B, Eiberg H, Kjer P, Rosenberg T (1996) Dominant optic atrophy mapped to chromosome 3q region. II. Clinical and epidemiological aspects. Acta Ophthalmol Scand 74: 3-7.

    PubMed  CAS  Google Scholar 

  • Kline LB, Glaser JS (1979) Dominant optic atrophy. The clinical profile. Arch Ophthalmol 97: 1680-1686.

    PubMed  CAS  Google Scholar 

  • Kok-van-Alphen CC (1970) Four families with the dominant infantile form of optic nerve atrophy. Acta Ophthalmol 48: 905-916.

    CAS  Google Scholar 

  • Leber T (1871) Ueber hereditare und kongenital-angelegte Sehnervenleiden. Graefes Arch Ophthalmol 17: 249-291.

    Google Scholar 

  • Livingstone IR, Mastaglia FL, Howe J, W Aherne GES (1980) Leber's optic neuropathy: clini-cal and visual evoked response studies in asymptomatic and symptomatic members of a 4-generation family. Br J Ophthalmol 64: 751-757.

    PubMed  CAS  Google Scholar 

  • Mackey D (1993) Blindness in offspring of women blinded by Leber's hereditary optic neuropathy (Letter). Lancet 341: 1020-1021.

    PubMed  CAS  Google Scholar 

  • Mackey D, Howell N (1992) A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology. Am J Hum Genet 51: 1218-1228.

    PubMed  CAS  Google Scholar 

  • Mackey DA, Oostra R, Rosenberg T, et al (1996) Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. Am J Hum Genet 59:481-485.

    PubMed  CAS  Google Scholar 

  • Man PYW, Turnbull DM, Chinnery PF (2002) Leber hereditary optic neuropathy. J Med Genet 39: 162-169.

    PubMed  CAS  Google Scholar 

  • Man PYW, Griffiths PG, Brown DT, Howell N, Turnbull DM (2003) The epidemiology of Leber hereditary optic neuropathy in the North East of England. Am J Hum Genet 72: 333-339.

    PubMed  CAS  Google Scholar 

  • Manchester PT, Calhoun FP (1958) Dominant hereditary optic atrophy with bitemporal field defects. Arch Ophthalmol 60: 479-484.

    Google Scholar 

  • Mantyjarvi MI, Nerdrum K, Tuppurainen K (1992) Colour vision in dominant optic atrophy. J Clin Neuro-Opthalmol 12: 98-103.

    CAS  Google Scholar 

  • Marchbank NJ, Craig JE, Leek JP, et al (2002) Deletion of the OPAl gene in a dominant optic atrophy family: evidence that haploinsufficiency is the cause of disease. J Med Genet 39: e47.

    PubMed  CAS  Google Scholar 

  • McLeod JG, Low PA, Morgan JA (1978) Charcot-Marie-Tooth disease with Leber optic atrophy. Neurology 28: 179-184.

    PubMed  CAS  Google Scholar 

  • McNaught AI, Allen JG, Healey D, Lal E (2000) Accuracy and implications of a reported family history of glaucoma: experience from the Glaucoma Inheritance Study in Tasmania. Arch Ophthalmol 118: 900-904.

    PubMed  CAS  Google Scholar 

  • Misaka T, Miyashita T, Kubo Y (2002) Primary structure of a dynamin-related mouse mitochondrial GTPase and its distribution in brain, subcellular localization and effect on mitochondrial morphology. J Biol Chem 277: 15834-15842.

    PubMed  CAS  Google Scholar 

  • Moller HU (1992) Recessively inherited, simple optic atrophy-does it exist? Ophthalmic Paediatr Genet 13: 31-32.

    PubMed  CAS  Google Scholar 

  • Nakamura M, Fujiwara Y, Yamamoto M (1993) The two locus control of Leber hereditary optic neuropathy and a high penetrance in Japanese pedigrees. Hum Genet 91: 339-341.

    PubMed  CAS  Google Scholar 

  • Newman NJ (1993) Leber's hereditary optic neuropathy. New genetic considerations. Arch Neurol 50: 540-548.

    PubMed  CAS  Google Scholar 

  • Newman NJ, Lott MT, Wallace DC (1991) The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am J Ophthalmol 111: 750-762.

    PubMed  CAS  Google Scholar 

  • Nikoskelainen E (1985) The clinical findings in Leber's hereditary optic neuropathy. Leber's disease. Trans Ophthalmol Soc UK 104: 845-852.

    PubMed  Google Scholar 

  • Nikoskelainen E, Hoyt WF, Nummelin K (1982) Ophthalmoscopic findings in Leber's here-ditary optic neuropathy. Fundus findings in asymptomatic family members. Arch Ophthalmol 100: 1597-1602.

    PubMed  CAS  Google Scholar 

  • Nikoskelainen E, Hoyt WF, Nimmelin K (1983) Ophthalmoscopic findings in Leber's heredi-tary optic neuropathy: the fundus findings in affected family members. Arch Ophthalmol 101: 1059-1068.

    PubMed  CAS  Google Scholar 

  • Nikoskelainen E, Wanne O, Dahl M (1985) Pre-excitation syndrome and Leber's hereditary optic neuropathy [letter]. Lancet 1: 696.

    PubMed  CAS  Google Scholar 

  • Nikoskelainen EK, Marttila RJ, Huoponen K, et al (1995) Leber's "plus": neurological abnor-malities in patients with Leber's hereditary optic neuropathy. J Neurol Neurosurg Psychiatry 59: 160-164.

    PubMed  CAS  Google Scholar 

  • Novotny EJ, Singh G, Wallace DC, et al (1986) Leber's disease and dystonia: a mitochondrial disease. Neurology 36: 1053-1060.

    PubMed  Google Scholar 

  • Olichon A, Emorine LJ, Descoins E, et al (2002) The human dynamin-related protein OPA is anchored to the mitochondrial inner membrane facing the inter-membrane space. FEBS Lett 523: 171-176.

    PubMed  CAS  Google Scholar 

  • Olsen NK, Hansen AW, Norby S, Edal AL, Jorgensen JR, Rosenberg T (1995) Leber's here-ditary optic neuropathy associated with a disorder indistinguishable from multiple sclerosis in a male harbouring the mitochondrial DNA 11778 mutation. Acta Neurol Scand 91: 326-329.

    PubMed  CAS  Google Scholar 

  • Oostra RJ, Bolhuis PA, Wijburg FA, Zorn-Ende G, Bleeker-Wagemakers EM (1994) Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome. J Med Genet 31: 280-286.

    PubMed  CAS  Google Scholar 

  • Oostra R-J, Kemp S, Bolhuis PA, Bleeker-Wagemakers EM (1996) No evidence of "skewed" inactivation of the X-chromosome as cause of Leber's hereditary optic neuropathy in female carriers. Hum Genet 97: 500-505.

    PubMed  CAS  Google Scholar 

  • Paulus W, Straube A, Bauer W, Harding AE (1993) Central nervous system involvement in Leber's hereditary optic neuropathy. J Neurol 240: 251-253.

    PubMed  CAS  Google Scholar 

  • Pegoraro E, Carelli V, Zeviani M, et al (1996) X-inactivation patterns in female Leber's here ditary optic neuropathy patients do not support a strong X-linked determinant Am J Med Genet 61: 356-362.

    PubMed  CAS  Google Scholar 

  • Pesch AEA, Leo-Kottler B, Mayer S, et al (2001) OPAl mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance. Hum Mol Gene 10: 1359-1368.

    CAS  Google Scholar 

  • Quigley HA (1996) Number of people with glaucoma worldwide. Br J Ophthalmol 80: 389-393.

    PubMed  CAS  Google Scholar 

  • Rezaie T, Child A, Hitchings R, et al (2002) Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science 295: 1077-1079.

    PubMed  CAS  Google Scholar 

  • Rice DS, Williams RW, Ward-Bailey P, et al (1995) Mapping the Bst mutation on mouse chromosome 16: a model for human optic atrophy. Mamm Genome 6: 546-548.

    PubMed  CAS  Google Scholar 

  • Rice DS, Tang Q, Williams RW, Harris BS, Davisson MT, Goldowitz D (1997). Decreased retinal ganglion cell number and misdirected axon growth associated with fissure defects in BSt/ + mutant mice. Invest Ophthalmol Vis Sci 38: 2112-2124.

    PubMed  CAS  Google Scholar 

  • Riordan-Eva P, Harding AE (1995) Leber's hereditary optic neuropathy: the clinical relevance of different mitochondrial DNA mutations. J Med Genet 32: 81-87.

    PubMed  CAS  Google Scholar 

  • Riordan-Eva P, Sanders MD, Govan GG, Sweeney MG, Costa JD, Harding AE (1995) The clinical features of Leber's hereditary optic neuropathy defined by the presence of a patho-genic mitochondrial DNA mutation. Brain 118: 319-337.

    PubMed  Google Scholar 

  • Rose FC, Bowden AN, Bowden PMA (1970) The heart in Leber's optic atrophy. Br J Ophthalmol 54: 388-393.

    PubMed  CAS  Google Scholar 

  • Ryan S, Arden GB (1988) Electrophysiological discrimination between retinal and optic nerve disorders. Doc Ophthalmol 68: 247-255.

    PubMed  CAS  Google Scholar 

  • Sadun AA, Win PH, Ross-Cisneros FN, Walker S, Carelli V (2000) Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve. Trans Am Ophthalmol Soc 98: 223-232.

    PubMed  CAS  Google Scholar 

  • Satoh M, Hamamoto T, Seo N, Kagawa Y, Endo H (2002) Differential sublocalization of the dynamin-related protein OPAl isoforms in mitochondria. Biochem Biophys Res Commun 300: 482-493.

    Google Scholar 

  • Simunovic M, Votruba M, Regan B, Mollon J (1998) Residual colour discrimination in low vision patients: results of a new test in dominant optic atrophy. Vision Res 38: 3413-3419.

    PubMed  CAS  Google Scholar 

  • Smith JL, Hoyt WF, Susac JO (1973) Ocular fundus in acute Leber's optic neuropathy. Arch Ophthalmol 90: 349-354.

    PubMed  CAS  Google Scholar 

  • Smith RS, John SW, Zabeleta A, Davisson MT, Hawes NL Chang B (2000) The bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularisation. Proc Natl Acad Sci USA 29: 2191-2195.

    Google Scholar 

  • Stoilov I, Akarsu AN, Sarfarazi M (1997) Identification of three truncating mutations in cytochrome P4501B1 (CYPIB1) as the principal cause of primary congenital glaucoma (buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum Mol Genet 6: 641-647.

    PubMed  CAS  Google Scholar 

  • Stoilova D, Child A, Desai SP, Sarfarazi M (1997) Refinement of the locus for autosomal dominant juvenile optic atrophy to a 2 cM region on 3q28. Ophthalmic Genet 18: 1-6.

    PubMed  CAS  Google Scholar 

  • Stone EM, Figert JH, Alward WLM, et al (1997) Identification of a gene that causes primary open angle glaucoma. Science 275: 668-670.

    PubMed  CAS  Google Scholar 

  • Sweeney MG, Davis MB, Lashwood A, Brockington M, Toscano A, Harding AE (1992) Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber's hereditary optic neuropathy. Am J Hum Genet 51: 741-748.

    PubMed  CAS  Google Scholar 

  • Thiselton DL, Alexander C, Morris A, et al (2001) A frameshift mutation in exon 28 of the OPAl gene explains the high prevalence of dominant optic atrophy in the Danish population: evidence for a founder effect. Hum Gene 109: 498-502.

    CAS  Google Scholar 

  • Thiselton DL, Alexander C, Taanman J-W, et al (2002) A comprehensive survey of mutations in the OPAl gene in patients with autosomal dominant optic atrophy (ADOA). Invest Ophthalmol Vis Sci 43: 1715-1724.

    PubMed  Google Scholar 

  • Toomes C, Marchbank NJ, Mackey DA, et al (2001) Spectrum, frequency and penetrance of OPAl mutations in dominant optic atrophy. Hum Mol Genet 10: 1369-1378.

    PubMed  CAS  Google Scholar 

  • Vickers JC, Craig JE, Stankovich J, et al (2002) The apolipoprotein e4 gene is associated with elevated risk of normal tension glaucoma. Mol Vision 8: 389-393.

    CAS  Google Scholar 

  • Vilkki J, Ott J, Savontaus M-L, Aula P, Nikoskelainen EK (1991) Optic atrophy in Leber hereditary optic neuropathy is probably determined by an X-chromosomal gene closely linked to DXS7. Am J Hum Genet 48: 486-491.

    PubMed  CAS  Google Scholar 

  • Volker-Dieben HJ, Lith GHMV, Went LN, Klawer JW, Staal A, De Vries-DeMol EC (1974) A family with sex linked optic atrophy (ophthalmological and neurological aspects). Doc Ophthalmol 37: 307-326.

    Google Scholar 

  • Votruba M, Moore AT, Bhattacharya SS (1997) Genetic refinement of dominant optic atrophy (OPA) locus to within a 2cM interval of chromosome 3q. J. Med Genet 34: 117-121.

    PubMed  CAS  Google Scholar 

  • Votruba M, Fitzke FW, Holder GE, Carter A, Bhattacharya SS, Moore AT (1998) Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy. Arch Ophthalmol 116: 351-358.

    PubMed  CAS  Google Scholar 

  • Votruba M, Leary S, Losseff N, Moore AT, Miller S, Moseley I (2000) Magnetic resonance imaging of the intraorbital optic nerve in patients with autosomal dominant optic atrophy. Neuroradiology 42: 180-183.

    PubMed  CAS  Google Scholar 

  • Votruba M, Thiselton D, Bhattacharya S (2003) Optic disc morphology of patients with OPAl autosomal dominant optic atrophy. Br J Ophthalmol 87: 48-53.

    PubMed  CAS  Google Scholar 

  • Waardenburg PJ (1957) Different types of hereditary optic atrophy. Acta Genet Statist Med 7: 287-290.

    PubMed  CAS  Google Scholar 

  • Wallace DC (1986) Mitotic segregation of mitochondrial DNAs in human cell hybrids and the expression of chloramphenicol resistance. Somat Cell Mol Genet 12: 41-49.

    PubMed  CAS  Google Scholar 

  • Wallace DC, Singh G, Lott MT, et al (1988) Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 242: 1427-1430.

    PubMed  CAS  Google Scholar 

  • Went LN, Mol ECDV-d, Volker-Dieben HJ (1975) A family with apparently sex-linked optic atrophy. J Med Genet 12: 94-98.

    PubMed  CAS  Google Scholar 

  • Wilson J (1965) Leber's hereditary optic neuropathy: a possible defect of cyanide metabolism. Clin Sci 29: 505-515.

    PubMed  CAS  Google Scholar 

  • Wissinger B, Besch D, Baumann B, et al (1997) Mutation analysis of the ND6 gene in patients with Leber's hereditary optic neuropathy. Biochem Biophys Res Commun 234: 511-515.

    PubMed  CAS  Google Scholar 

  • Wolfs RC, Klaver CC, Ramrattan RS, vanDuijn CM, Hofman A, deJong PT (1998) Genetic risk of primary open angle glaucoma. Arch Ophthalmol 116: 1640-1645.

    PubMed  CAS  Google Scholar 

  • WuDunn D (2002) Genetic basis of glaucoma. Curr Opin Ophthalmol 13: 55-60.

    PubMed  Google Scholar 

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  1. Department of Molecular Genetics, Institute of Ophthalmology, London

    M. Votruba, S. Aijaz & A. T. Moore

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  1. M. Votruba
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  2. S. Aijaz
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  3. A. T. Moore
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Correspondence to M. Votruba.

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Votruba, M., Aijaz, S. & Moore, A.T. A review of primary hereditary optic neuropathies. J Inherit Metab Dis 26, 209–227 (2003). https://doi.org/10.1023/A:1024441302074

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