SURF1 , encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome

• Published in: Nature genetics Vol. 20; no. 4; pp. 337 - 343
• Main Authors: Shoubridge, Eric A, Zhu, Zhiqing, Yao, Jianbo, Johns, Timothy, Fu, Katherine, Bie, Isabelle De, Macmillan, Carol, Cuthbert, Andrew P, Newbold, Robert F, Wang, Jia-chi, Chevrette, Mario, Brown, Garry K, Brown, Ruth M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-12-1998
• Subjects: Amino Acid Sequence; Biological and medical sciences; Cell Line; Chromosome Mapping; Chromosomes, Human, Pair 9; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA, Complementary; Electron Transport Complex IV - biosynthesis; Humans; In Situ Hybridization, Fluorescence; Leigh Disease - genetics; Medical sciences; Membrane Proteins; Mitochondrial Proteins; Molecular Sequence Data; Mutation; Neurology; Proteins - genetics; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid; Genetic mapping; Human; Nervous system diseases; Enzyme; Leigh disease; Deficiency; Cytochrome-c oxidase; Metabolic diseases; Enzymopathy; Chromosome C9; Cerebral disorder; Genetic disease; Respiratory chain; Enzymatic activity; Central nervous system disease; Complementation; Oxidoreductases; Mutation
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/3804

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.