Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder

Gavin Hudson, Sharon Keers, Patrick Yu Wai Man, Philip Griffiths, Kirsi Huoponen, Marja Liisa Savontaus, Eeva Nikoskelainen, Massimo Zeviani, Franco Carrara, Rita Horvath, V. Karcagi, Liesbeth Spruijt, I. F M De Coo, Hubert J M Smeets, Patrick F. Chinnery

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Mitochondrial DNA (mtDNA) mutations are a major cause of human disease. A large number of different molecular defects ultimately compromise oxidative phosphorylation, but it is not clear why the same biochemical defect can cause diverse clinical phenotypes. There is emerging evidence that nuclear genes modulate the phenotype of primary mtDNA disorders. Here, we define an X-chromosomal haplotype that interacts with specific MTND mutations to cause visual failure in the most common mtDNA disease, Leber hereditary optic neuropathy. This effect is independent of the mtDNA genetic background and explains the variable penetrance and sex bias that characterizes this disorder.

Original languageEnglish
Pages (from-to)1086-1091
Number of pages6
JournalAmerican Journal of Human Genetics
Volume77
Issue number6
DOIs
Publication statusPublished - Dec 2005

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Mitochondrial Diseases
Mitochondrial DNA
Haplotypes
Phenotype
Leber's Hereditary Optic Atrophy
Sexism
Mutation
Penetrance
Oxidative Phosphorylation
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Hudson, G., Keers, S., Man, P. Y. W., Griffiths, P., Huoponen, K., Savontaus, M. L., ... Chinnery, P. F. (2005). Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. American Journal of Human Genetics, 77(6), 1086-1091. https://doi.org/10.1086/498176

Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. / Hudson, Gavin; Keers, Sharon; Man, Patrick Yu Wai; Griffiths, Philip; Huoponen, Kirsi; Savontaus, Marja Liisa; Nikoskelainen, Eeva; Zeviani, Massimo; Carrara, Franco; Horvath, Rita; Karcagi, V.; Spruijt, Liesbeth; De Coo, I. F M; Smeets, Hubert J M; Chinnery, Patrick F.

In: American Journal of Human Genetics, Vol. 77, No. 6, 12.2005, p. 1086-1091.

Research output: Contribution to journalArticle

Hudson, G, Keers, S, Man, PYW, Griffiths, P, Huoponen, K, Savontaus, ML, Nikoskelainen, E, Zeviani, M, Carrara, F, Horvath, R, Karcagi, V, Spruijt, L, De Coo, IFM, Smeets, HJM & Chinnery, PF 2005, 'Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder', American Journal of Human Genetics, vol. 77, no. 6, pp. 1086-1091. https://doi.org/10.1086/498176
Hudson, Gavin ; Keers, Sharon ; Man, Patrick Yu Wai ; Griffiths, Philip ; Huoponen, Kirsi ; Savontaus, Marja Liisa ; Nikoskelainen, Eeva ; Zeviani, Massimo ; Carrara, Franco ; Horvath, Rita ; Karcagi, V. ; Spruijt, Liesbeth ; De Coo, I. F M ; Smeets, Hubert J M ; Chinnery, Patrick F. / Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. In: American Journal of Human Genetics. 2005 ; Vol. 77, No. 6. pp. 1086-1091.
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