Severe lactic acidosis caused by a novel frame-shift mutation in mitochondrial-encoded cytochrome c oxidase subunit II

Am J Med Genet. 2001 Jul 22;102(1):95-9. doi: 10.1002/1096-8628(20010722)102:1<95::aid-ajmg1412>;2-u.


We report the first frame-shift truncation mutation in a mitochondrial DNA (mtDNA)-encoded subunit II of cytochrome c oxidase (COXII). The mutation was identified by temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing in an infant who died at 12 days of age following a course of apnea, bradycardia, and severe lactic acidosis. The patient had a twin brother who died at two days of age of similar course. The mutation, 8042delAT, produced a truncated protein that was 72 amino acids shorter than the wild type protein. The mutant protein, missing one third of the amino acid residues at the C-terminal essential for hydrophilic interaction with cytochrome c, ligand binding to CuA and Mg, and the formation of proton and water channels, apparently has devastating effects on mitochondrial respiratory function.

Publication types

  • Case Reports

MeSH terms

  • Acidosis, Lactic / genetics*
  • Acidosis, Lactic / pathology
  • Base Sequence
  • DNA Mutational Analysis
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics*
  • Family Health
  • Fatal Outcome
  • Female
  • Frameshift Mutation
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Male
  • Pedigree


  • DNA, Mitochondrial
  • Electron Transport Complex IV