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.
Pubmed ID: 9837813 RIS Download
Mesh terms: Animals | 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
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