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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1998 Dec;63(6):1609–1621. doi: 10.1086/302150

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

V Tiranti 1, K Hoertnagel 1, R Carrozzo 1, C Galimberti 1, M Munaro 1, M Granatiero 1, L Zelante 1, P Gasparini 1, R Marzella 1, M Rocchi 1, M P Bayona-Bafaluy 1, J A Enriquez 1, G Uziel 1, E Bertini 1, C Dionisi-Vici 1, B Franco 1, T Meitinger 1, M Zeviani 1
PMCID: PMC1377632  PMID: 9837813

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.

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Selected References

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