Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency.

TitleMutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency.
Publication TypeJournal Article
Year of Publication1998
AuthorsTiranti, V, Hoertnagel, K, Carrozzo, R, Galimberti, C, Munaro, M, Granatiero, M, Zelante, L, Gasparini, P, Marzella, R, Rocchi, M, Bayona-Bafaluy, MP, Enriquez, JA, Uziel, G, Bertini, E, Dionisi-Vici, C, Franco, B, Meitinger, T, Zeviani, M
JournalAm J Hum Genet
Date Published1998 Dec
KeywordsAnimals, Cell Fusion, Cell Line, Chromosomes, Human, Pair 9, Cricetinae, Cytochrome-c Oxidase Deficiency, DNA Mutational Analysis, DNA, Mitochondrial, Electron Transport Complex IV, Exons, Female, Fibroblasts, Genetic Complementation Test, Genotype, Humans, Hybrid Cells, In Situ Hybridization, Fluorescence, Leigh Disease, Lod Score, Male, Membrane Proteins, Mice, Mitochondrial Proteins, Molecular Sequence Data, Mutation, Pedigree, Proteins, Rho Factor, Telomere

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.

Alternate JournalAm. J. Hum. Genet.
Citation Key10.1086/302150
PubMed ID9837813
PubMed Central IDPMC1377632
Grant List767 / / Telethon / Italy
TGM00Z11 / / Telethon / Italy
TGM06S01 / / Telethon / Italy