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

  • V Tiranti
  • K Hoertnagel
  • R Carrozzo
  • C Galimberti
  • M Munaro
  • M Granatiero
  • L Zelante
  • P Gasparini
  • R Marzella
  • M Rocchi
  • M P Bayona-Bafaluy
  • J A Enriquez
  • G Uziel
  • E Bertini
  • C Dionisi-Vici
  • B Franco
  • T Meitinger
  • M Zeviani
Publication Date
Dec 01, 1998
  • Biology
  • Medicine


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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