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, Veronika Karcagi, Liesbeth Spruijt, I. F.M. De Coo, Hubert J.M. Smeets, Patrick F. Chinnery

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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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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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., & 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