Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy

Am J Hum Genet. 2000 Nov;67(5):1104-9. doi: 10.1016/S0002-9297(07)62940-1. Epub 2000 Sep 28.


Cytochrome c oxidase (COX) catalyzes both electron transfer from cytochrome c to molecular oxygen and the concomitant vectorial proton pumping across the inner mitochondrial membrane. Studying a large family with multiple cases of neonatal ketoacidotic comas and isolated COX deficiency, we have mapped the disease locus to chromosome 17p13.1, in a region encompassing two candidate genes involved in COX assembly-namely, SCO1 and COX10. Mutation screening revealed compound heterozygosity for SCO1 gene mutations in the patients. The mutated allele, inherited from the father, harbored a 2-bp frameshift deletion (DeltaGA; nt 363-364) resulting in both a premature stop codon and a highly unstable mRNA. The maternally inherited mutation (C520T) changed a highly conserved proline into a leucine in the protein (P174L). This proline, adjacent to the CxxxC copper-binding domain of SCO1, is likely to play a crucial role in the tridimentional structure of the domain. Interestingly, the clinical presentation of SCO1-deficient patients markedly differs from that of patients harboring mutations in other COX assembly and/or maturation genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Amino Acid Sequence
  • Base Sequence
  • Chromosomes, Human, Pair 17 / genetics
  • Cytochrome-c Oxidase Deficiency*
  • DNA Mutational Analysis
  • Electron Transport
  • Electron Transport Complex IV / genetics*
  • Electron Transport Complex IV / metabolism
  • Female
  • Humans
  • Infant, Newborn
  • Liver / enzymology
  • Liver / metabolism
  • Liver Failure / complications*
  • Liver Failure / enzymology
  • Liver Failure / genetics
  • Liver Failure / metabolism
  • Male
  • Metabolism, Inborn Errors / complications*
  • Metabolism, Inborn Errors / enzymology
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / metabolism
  • Molecular Sequence Data
  • Muscles / enzymology
  • Muscles / metabolism
  • Mutation / genetics*
  • Pedigree
  • Sequence Alignment


  • Electron Transport Complex IV