Clinical spectrum of Leber's hereditary optic neuropathy.
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.
Kerrison
J B
JB
Neuro-Ophthalmology Unit, Emory Eye Center, Atlanta, GA 30322, USA.
Newman
N J
NJ
D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics; D015418:Optic Atrophies, Hereditary / Q000235:genetics / Q000473:pathology*; D017354:Point Mutation
D004272:DNA, Mitochondrial