No mitochondrial cytochrome oxidase (COX) gene mutations in 18 cases of COX deficiency

Hum Genet. 1997 Dec;101(2):247-50. doi: 10.1007/s004390050625.


Cytochrome c oxidase (COX) deficiency causes a variety of neuromuscular and non-neuromuscular disorders in childhood and adulthood and can theoretically undergo either a nuclear or a mitochondrial (mt) mode of inheritance, making genetic counseling in COX deficiency particularly hazardous. In an attempt to determine the respective roles of mtDNA and nuclear DNA mutations in COX deficiency, we sequenced the three mitochondrially encoded COX subunits (COXI-III) in a series of 18 patients with isolated COX deficiency, especially as COXI-III code for the catalytic site of the enzyme. We failed to detect any deleterious mutations in this series. Moreover, no mtDNA deletion was observed and sequencing of the flanking tRNA genes involved in the maturation of the COX transcripts failed to detect deleterious mutations as well. The present study supports the view that the disease-causing mutations do not lie in the mt genome but, rather, in the nuclear genes encoding either the COX subunits or the proteins involved in assembly of the complex and suggests a recurrent risk of 25% rather than other modes of inheritance in COX deficiencies.

MeSH terms

  • Cell Nucleus / genetics
  • Cytochrome-c Oxidase Deficiency*
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics*
  • Humans
  • Mitochondria / enzymology
  • Mitochondria / genetics*
  • Mitochondrial Myopathies / genetics
  • Mutation*
  • Polymorphism, Genetic


  • DNA, Mitochondrial
  • Electron Transport Complex IV