An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy

Am J Hum Genet. 1999 May;64(5):1330-9. doi: 10.1086/302361.


A novel heteroplasmic 7587T-->C mutation in the mitochondrial genome which changes the initiation codon of the gene encoding cytochrome c oxidase subunit II (COX II), was found in a family with mitochondrial disease. This T-->C transition is predicted to change the initiating methionine to threonine. The mutation load was present at 67% in muscle from the index case and at 91% in muscle from the patient's clinically affected son. Muscle biopsy samples revealed isolated COX deficiency and mitochondrial proliferation. Single-muscle-fiber analysis revealed that the 7587C copy was at much higher load in COX-negative fibers than in COX-positive fibers. After microphotometric enzyme analysis, the mutation was shown to cause a decrease in COX activity when the mutant load was >55%-65%. In fibroblasts from one family member, which contained >95% mutated mtDNA, there was no detectable synthesis or any steady-state level of COX II. This new mutation constitutes a new mechanism by which mtDNA mutations can cause disease-defective initiation of translation.

Publication types

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

MeSH terms

  • Adult
  • Codon, Initiator / genetics*
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics*
  • Electron Transport Complex IV / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Encephalomyopathies / enzymology
  • Mitochondrial Encephalomyopathies / genetics*
  • Point Mutation / genetics*
  • Protein Biosynthesis
  • RNA, Messenger / analysis
  • RNA, Transfer, Asp / genetics
  • RNA, Transfer, Ser / genetics


  • Codon, Initiator
  • DNA, Mitochondrial
  • RNA, Messenger
  • RNA, Transfer, Asp
  • RNA, Transfer, Ser
  • cytochrome C oxidase subunit II
  • Electron Transport Complex IV