SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome

Nat Genet. 1998 Dec;20(4):337-43. doi: 10.1038/3804.

Abstract

Leigh Syndrome (LS) is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency. COX deficiency is an autosomal recessive trait and most patients belong to a single genetic complementation group. DNA sequence analysis of the genes encoding the structural subunits of the COX complex has failed to identify a pathogenic mutation. Using microcell-mediated chromosome transfer, we mapped the gene defect in this disorder to chromosome 9q34 by complementation of the respiratory chain deficiency in patient fibroblasts. Analysis of a candidate gene (SURF1) of unknown function revealed several mutations, all of which predict a truncated protein. These data suggest a role for SURF1 in the biogenesis of the COX complex and define a new class of gene defects causing human neurodegenerative disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Chromosome Mapping
  • Chromosomes, Human, Pair 9
  • DNA, Complementary
  • Electron Transport Complex IV / biosynthesis*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leigh Disease / genetics*
  • Membrane Proteins
  • Mitochondrial Proteins
  • Molecular Sequence Data
  • Mutation*
  • Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid

Substances

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