CLINICAL SPECTRUM OF LEBERS HEREDITARY OPTIC NEUROPATHY

Leber's hereditary optic neuropathy (LHON) is a bilateral subacute opt ic 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 I of the respiratory chain. Mole cular diagnosis has expanded the spectrum of the LHON phenotype and pr ompted investigation into optic neuropathies due to demyelinating dise ase, glaucoma, tobacco/alcohol amblyopia, and nutritional optic neurop athy. While mitochondrial mutations are required for LHON disease expr ession, other genetic or epigentic factors must play a role in disease penetrance and expression. Proposed determinants of disease include h eteroplasmy, an X-linked vision loss susceptibility locus, environment al factors, and secondary mitochondrial mutations. (C) 1997 Wiley-Liss , Inc.