title: SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome.
abstract: Leigh 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.
authors.affiliation: Montreal Neurological Institute, Quebec, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Yao
authors.forename: T
authors.initials: T
authors.lastname: Johns
authors.forename: K
authors.initials: K
authors.lastname: Fu
authors.forename: I
authors.initials: I
authors.lastname: De Bie
authors.forename: C
authors.initials: C
authors.lastname: Macmillan
authors.forename: A P
authors.initials: AP
authors.lastname: Cuthbert
authors.forename: R F
authors.initials: RF
authors.lastname: Newbold
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Chevrette
authors.forename: G K
authors.initials: GK
authors.lastname: Brown
authors.forename: R M
authors.initials: RM
authors.lastname: Brown
authors.forename: E A
authors.initials: EA
authors.lastname: Shoubridge
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D018076:DNA, Complementary; D003576:Electron Transport Complex IV / Q000096:biosynthesis*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007888:Leigh Disease / Q000235:genetics*; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C092928:Surf-1 protein; D003576:Electron Transport Complex IV