Nature Genetics
20, 337 - 343 (1998)
doi:10.1038/3804
SURF1, encoding a factor involved in the biogenesis of cytochrome
c oxidase, is mutated in Leigh syndromeZhiqing Zhu1, 6, Jianbo Yao1, 6, Timothy Johns1, Katherine Fu1, Isabelle De Bie1, Carol Macmillan1, Andrew P. Cuthbert3, Robert F. Newbold3, Jia-chi Wang4, Mario Chevrette4, Garry K. Brown5, Ruth M. Brown5
& Eric A. Shoubridge.1, 21
Montreal Neurological Institute, 3801
University Street, Montreal, Quebec, Canada
H3A 2B4. 2
Department of Human Genetics, 1205 avenue
Dr. Penfield, McGill University, Montreal, Quebec,
Canada H3A 1B1. 3
Department of Biology and Biochemistry, Brunel University,
Uxbridge, UK. 4
Montreal General Hospital Research Institute, Department
of Surgery, Urology Division, McGill University, Montreal,
Canada. 5
Genetics Unit, Department of Biochemistry, Oxford University,
South Parks Road, Oxford, U.K.
6
These authors contributed equally to this work.
Correspondence should be addressed to Eric A. Shoubridge. eric@ericpc.mni.mcgill.caLeigh Syndrome (LS) is a severe neurological disorder characterized by
bilaterally symmetrical necrotic lesions in subcortical brain regions that
is commonly associated with systemic cytochrome c oxidase (COX) deficiency.
COX deficiency is an autosomal recessive trait and most patients belong to
a single genetic complementation group. DNA sequence analysis of the genes
encoding the structural subunits of the COX complex has failed to identify
a pathogenic mutation. Using microcell-mediated chromosome transfer, we mapped
the gene defect in this disorder to chromosome 9q34 by complementation of
the respiratory chain deficiency in patient fibroblasts. Analysis of a candidate
gene (SURF1) of unknown function revealed several mutations, all of
which predict a truncated protein. These data suggest a role for SURF1 in
the biogenesis of the COX complex and define a new class of gene defects causing
human neurodegenerative disease.
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