A microdeletion in cytochrome c oxidase (COX) subunit III associated with COX deficiency and recurrent myoglobinuria

Nat Genet. 1996 Apr;12(4):410-6. doi: 10.1038/ng0496-410.


We have identified a 15-bp microdeletion in a highly conserved region of the mitochondrially encoded gene for cytochrome c oxidase (COX) subunit III in a patient with severe isolated COX deficiency and recurrent myoglobinuria. The mutant mitochondrial DNA (mtDNA) comprised 92% of the mtDNA in muscle and 0.7% in leukocytes. Immunoblots and immunocytochemistry suggested a lack of assembly or instability of the complex. Microdissected muscle fibres revealed significantly higher portions of mutant mtDNA in COX-negative than in COX-positive fibres. This represents the first case of isolated COX deficiency to be defined at the molecular level.

Publication types

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

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cytochrome-c Oxidase Deficiency*
  • DNA / genetics
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex IV / chemistry
  • Electron Transport Complex IV / genetics*
  • Female
  • Genotype
  • Histocytochemistry
  • Humans
  • Molecular Sequence Data
  • Muscle, Skeletal / enzymology
  • Myoglobinuria / enzymology*
  • Myoglobinuria / genetics*
  • Phenotype
  • Protein Conformation
  • Recurrence
  • Sequence Deletion*
  • Sequence Homology, Amino Acid


  • DNA, Mitochondrial
  • DNA
  • Electron Transport Complex IV

Associated data

  • GENBANK/U35430