A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I

Am J Hum Genet. 1992 Aug;51(2):378-85.


A G-to-A transition at nucleotide pair (np) 7444 in the mtDNA was found to correlate with Leber hereditary optic neuropathy (LHON). The mutation eliminates the termination codon of the cytochrome c oxidase subunit I (COI) gene, extending the COI polypeptide by three amino acids. The mutation was discovered as an XbaI restriction-endonuclease-site loss present in 2 (9.1%) of 22 LHON patients who lacked the np 11778 LHON mutation and in 6 (1.1%) of 545 unaffected controls. The mutant polypeptide has an altered mobility on SDS-PAGE, suggesting a structural alteration, and the cytochrome c oxidase enzyme activity of patient lymphocytes is reduced approximately 40% relative to that in controls. These data suggest that the np 7444 mutation results in partial respiratory deficiency and thus contributes to the onset of LHON.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics*
  • Electron Transport Complex IV / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Optic Atrophies, Hereditary / enzymology
  • Optic Atrophies, Hereditary / genetics*
  • Phylogeny
  • Terminator Regions, Genetic


  • DNA, Mitochondrial
  • Electron Transport Complex IV