Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene

Ann Neurol. 2001 Sep;50(3):409-13. doi: 10.1002/ana.1141.


We report the first nonsense mutation (G7896A) in the mtDNA gene for subunit II of cytochrome c oxidase (COX) in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heteroplasmic in muscle, blood, and fibroblasts from the patient and abundantly present in COX-deficient fibers, but less abundant in COX-positive fibers; it was not found in blood samples from the patient's asymptomatic maternal relatives. Immunoblot analysis showed a reduced concentration of both COX II and COX I polypeptides, suggesting impaired assembly of COX holoenzyme.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Codon, Nonsense / genetics*
  • DNA, Mitochondrial / biosynthesis
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics*
  • Electron Transport Complex IV / metabolism
  • Female
  • Humans
  • Mitochondrial Myopathies / enzymology
  • Mitochondrial Myopathies / genetics*
  • Muscle, Skeletal / enzymology
  • Phenotype
  • Polymorphism, Restriction Fragment Length


  • Codon, Nonsense
  • DNA, Mitochondrial
  • cytochrome C oxidase subunit II
  • Electron Transport Complex IV