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

Am J Hum Genet. 1998 Dec;63(6):1609-21. doi: 10.1086/302150.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Fusion / genetics
  • Cell Line
  • Chromosomes, Human, Pair 9 / genetics
  • Cricetinae
  • Cytochrome-c Oxidase Deficiency*
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex IV / genetics
  • Exons / genetics
  • Female
  • Fibroblasts
  • Genetic Complementation Test
  • Genotype
  • Humans
  • Hybrid Cells
  • In Situ Hybridization, Fluorescence
  • Leigh Disease / genetics*
  • Leigh Disease / metabolism
  • Lod Score
  • Male
  • Membrane Proteins
  • Mice
  • Mitochondrial Proteins
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Proteins / genetics*
  • Proteins / metabolism
  • Rho Factor / genetics
  • Telomere / genetics


  • DNA, Mitochondrial
  • Membrane Proteins
  • Mitochondrial Proteins
  • Proteins
  • Rho Factor
  • Surf-1 protein
  • Electron Transport Complex IV

Associated data

  • GENBANK/Z35093