Abstract
Leber's hereditary optic neuropathy (LHON), which is associated with mutations in mitochondrial DNA (mtDNA), is commoner in males than females. A study of over 30 LHON families with a mutation at position 3460 of mtDNA demonstrates a significantly decreased male excess from that generally quoted, with evidence for a marked bias in the ascertainment of males over females. This has implications for the analysis of those factors which give rise to the male bias.
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Huoponen K, Vilkki J, Aula P, Nikoskelainen EK, Savontaus M-L . A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy. Am J Hum Genet 1991;48:1147–53.
Howell N, Bindoff LA, McCullough DA, Kubacka I, Poulton J, Mackey D, et al. Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. Am J Hum Genet 1991;49:939–50.
Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AMS, Elsas LJ . Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 1988;242:1427–30.
Mackey D, Howell N . A variant of Leber hereditary optic neuropathy characterised by recovery of vision and by an unusual mitochondrial genetic etiology. Am J Hum Genet 1992;51:1218–28.
Howell N, Halvorson S, Burns J, McCullough DA, Poulton J . When does bilateral optic atrophy become Leber Hereditary Optic Neuropathy? Am J Hum Genet 1993;53:959–63.
Bell J . The treasury of human inheritance, vol. II, part 4. Cambridge: Cambridge University Press, 1931.
Lundsgaard R . Leber's disease: a genealogic, genetic and clinical study of 101 cases of retrobulbar optic neuritis in 20 Danish families. Dissertation, Copenhagen, 1944.
van Senus AHC . Leber's disease in the Netherlands. Dissertation, Rotterdam, 1963.
Maniatis T, Fritch EF, Sambrook J . Molecular cloning: a laboratory manual. New York: Cold Spring Harbor Laboratory, 1982.
Tobal K, Layton DM, Mufti GJ . A non-invasive isolation of constitutional DNA for genetic analysis. Lancet 1989;i:1281.
Bu X, Rotter JI . X-chromosome linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence of X chromosome inactivation. Proc Natl Acad Sci USA 1991;88:8198–202.
Chen JD, Cox I, Denton MJ . Preliminary exclusion of an X-linked gene in Leber optic atrophy by linkage analysis. Hum Genet 1989;82:203–7.
Carvalho MRS, Muller B, Rozer E, Berninger T, Kommereil G, Blankenagel A, et al. Leber hereditary optic neuroretinopathy and the X-chromosomal susceptibility factor: no linkage to DXS7. Hum Hered 1992;42:316–20.
Sweeney MG, Davis MB, Lashwood AM, Brockington M, Toscano A, Harding AE . Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy. Am J Hum Genet 1992;51:741–8.
Juvonen V, Vilkki J, Aula J, Nikoskelainen P, Savontaus M-L . Reevaluation of the linkage of an optic atrophy susceptibility gene to X-chromosomal markers in Finnish families with Leber hereditary optic neuroretinopathy (LHON). Am J Hum Genet 1993;53:289–92.
Brown MD, Voljavac AS, Lott MT, Torroni A, Yang C-C, Wallace DC . Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy. Genetics 1992;130:163–73.
Ott J, Bhattacharya S, Chen JD, et al. Localising multiple X chromosome-linked retinitis pigmentosa loci using multilocus homogeneity tests. Proc Natl Acad Sci USA 1990;87:701–4.
Day CE, Scheffler IE . Mapping of the genes of some of the components of the electron chain (complex I) on the X chromosome of mammals. Somat Cell Genet 1982;8:691–707.
Johns DR, Smith KH, Miller NR . Leber's hereditary optic neuropathy: clinical manifestations of the 3460 mutation. Arch Ophthalmol 1992;110:1577–81.
Oostra RJ, Bolhuis PA, Zorn-Ende G, De KokNazaruh MM, Bleeker-Wagemakers EM . Leber's hereditary optic neuropathy: no significant evidence for primary or secondary pathogenicity of the 15 257 mutation. Hum Genet 1995;(in press).
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Black, G., Craig, I., Oostra, R. et al. Leber's hereditary optic neuropathy: Implications of the sex ratio for linkage studies in families with the 3460 ND1 mutation. Eye 9, 513–516 (1995). https://doi.org/10.1038/eye.1995.117
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DOI: https://doi.org/10.1038/eye.1995.117
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