title: Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency.
abstract: Leigh disease associated with cytochrome c oxidase deficiency (LD[COX-]) is one of the most common disorders of the mitochondrial respiratory chain, in infancy and childhood. No mutations in any of the genes encoding the COX-protein subunits have been identified in LD(COX-) patients. Using complementation assays based on the fusion of LD(COX-) cell lines with several rodent/human rho0 hybrids, we demonstrated that the COX phenotype was rescued by the presence of a normal human chromosome 9. Linkage analysis restricted the disease locus to the subtelomeric region of chromosome 9q, within the 7-cM interval between markers D9S1847 and D9S1826. Candidate genes within this region include SURF-1, the yeast homologue (SHY-1) of which encodes a mitochondrial protein necessary for the maintenance of COX activity and respiration. Sequence analysis of SURF-1 revealed mutations in numerous DNA samples from LD(COX-) patients, indicating that this gene is responsible for the major complementation group in this important mitochondrial disorder.
authors.affiliation: Istituto Nazionale Neurologico, Divisione di Biochimica e Genetica, 20133 Milano, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Tiranti
authors.forename: K
authors.initials: K
authors.lastname: Hoertnagel
authors.forename: R
authors.initials: R
authors.lastname: Carrozzo
authors.forename: C
authors.initials: C
authors.lastname: Galimberti
authors.forename: M
authors.initials: M
authors.lastname: Munaro
authors.forename: M
authors.initials: M
authors.lastname: Granatiero
authors.forename: L
authors.initials: L
authors.lastname: Zelante
authors.forename: P
authors.initials: P
authors.lastname: Gasparini
authors.forename: R
authors.initials: R
authors.lastname: Marzella
authors.forename: M
authors.initials: M
authors.lastname: Rocchi
authors.forename: M P
authors.initials: MP
authors.lastname: Bayona-Bafaluy
authors.forename: J A
authors.initials: JA
authors.lastname: Enriquez
authors.forename: G
authors.initials: G
authors.lastname: Uziel
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: C
authors.initials: C
authors.lastname: Dionisi-Vici
authors.forename: B
authors.initials: B
authors.lastname: Franco
authors.forename: T
authors.initials: T
authors.lastname: Meitinger
authors.forename: M
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D000818:Animals; D002459:Cell Fusion / Q000235:genetics; D002460:Cell Line; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D006224:Cricetinae; D030401:Cytochrome-c Oxidase Deficiency; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005347:Fibroblasts; D005816:Genetic Complementation Test; D005838:Genotype; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D007888:Leigh Disease / Q000235:genetics* / Q000378:metabolism; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012234:Rho Factor / Q000235:genetics; D016615:Telomere / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012234:Rho Factor; C092928:Surf-1 protein; D003576:Electron Transport Complex IV