Mitochondrial DNA mutations associated with the 11778 mutation in Leber's disease

To clarify the characteristics of possible synergestic mitochondrial DNA (mtDNA) mutations associated with Leber's hereditary optic neuropathy (LHON), we analyzed the entire nucleotide sequences of mitochondrial 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 mutations in the mtDNA in addition to the 11778 mutation. Two nucleotide substitutions, an A-to-G transition at position 856 in the 12S rRNA gene and an A-to-G transition at 14692 in the T psi C loop of the tRNA(Glu) gene, occurred at highly conserved sites among various species. These mutations in combination with the 11778 mutation might synergetically contribute to the pathogenesis of LHON.