Clinical spectrum of Leber's hereditary optic neuropathy

Clin Neurosci. 1997;4(5):295-301.


Leber's hereditary optic neuropathy (LHON) is a bilateral subacute optic neuropathy caused by mutations in the mitochondrial genome. Primary mutations are located at nucleotide positions 3460, 11778, and 14484 in genes encoding subunits of Complex 1 of the respiratory chain. Molecular diagnosis has expanded the spectrum of the LHON phenotype and prompted investigation into optic neuropathies due to demyelinating disease, glaucoma, tobacco/alcohol amblyopia, and nutritional optic neuropathy. While mitochondrial mutations are required for LHON disease expression, other genetic or epigentic factors must play a role in disease penetrance and expression. Proposed determinants of disease include heteroplasmy, an X-linked vision loss susceptibility locus, environmental factors, and secondary mitochondrial mutations.

Publication types

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

MeSH terms

  • DNA, Mitochondrial / genetics
  • Humans
  • Mitochondria / genetics
  • Optic Atrophies, Hereditary / genetics
  • Optic Atrophies, Hereditary / pathology*
  • Point Mutation


  • DNA, Mitochondrial