Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy

Science. 1988 Dec 9;242(4884):1427-30. doi: 10.1126/science.3201231.


Leber's hereditary optic neuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.

Publication types

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

MeSH terms

  • Animals
  • Arginine
  • Black People
  • Cytochrome Reductases / genetics*
  • DNA, Mitochondrial / genetics*
  • Female
  • Genes*
  • Georgia
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Histidine
  • Humans
  • Macromolecular Substances
  • Male
  • Mutation*
  • NADH Dehydrogenase / genetics*
  • Optic Atrophies, Hereditary / genetics*
  • Pedigree
  • Reference Values
  • White People


  • DNA, Mitochondrial
  • Macromolecular Substances
  • Histidine
  • Arginine
  • Cytochrome Reductases
  • NADH Dehydrogenase