MITOCHONDRIAL-DNA MUTATIONS ASSOCIATED WITH THE 11778-MUTATION IN LEBERS-DISEASE

To clarify the characteristics of possible synergestic mitochondrial D NA (mtDNA) mutations associated with Leber's hereditary optic neuropat hy (LHON), we analyzed the entire nucleotide sequences of mitochondria l genome of two Japanese patients from independent pedigrees harboring the 11778 mtDNA mutation, and compared their sequences with those of 47 disease and 6 normal controls. We have detected several unique muta tions in the mtDNA in addition to the 11778 mutation. Two nucleotide s ubstitutions, an A-to-G transition at position 856 in the 12S rRNA gen e and an A-to-G transition at 14692 in the T psi C loop of the tRNA(Gl u) gene, occurred at highly conserved sites among various species. The se mutations in combination with the 11778 mutation might synergetical ly contribute to the pathogenesis of LHON.