TY - JOUR
T1 - Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder
AU - Hudson, Gavin
AU - Keers, Sharon
AU - Man, Patrick Yu Wai
AU - Griffiths, Philip
AU - Huoponen, Kirsi
AU - Savontaus, Marja Liisa
AU - Nikoskelainen, Eeva
AU - Zeviani, Massimo
AU - Carrara, Franco
AU - Horvath, Rita
AU - Karcagi, Veronika
AU - Spruijt, Liesbeth
AU - De Coo, I. F M
AU - Smeets, Hubert J M
AU - Chinnery, Patrick F.
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
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U2 - 10.1086/498176
DO - 10.1086/498176
M3 - Article
C2 - 16380918
AN - SCOPUS:28144454984
VL - 77
SP - 1086
EP - 1091
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 6
ER -