Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Leber's hereditary optic neuropathy has been linked to a mitochondrial DNA mutation at position 11,778 in the ND-4 gene in 50% of families. Three alternative mutations in Complex I genes at positions 4,216 (ND-1), 4,917 (ND-2), and 13,708 (ND-5) were discovered in 11,778- Leber families. The 4,917 and 13,708 mutations appear pathogenetically significant and were observed in 36% (4,917 mutation) and 43% (13,708 mutation) of 11,778- Leber probands. Multiple, simultaneous mutations were noted. Mutation of distinct, functionally related Complex I genes is the central pathogenetic feature of Leber's hereditary optic neuropathy.