[Genetic characteristics of Japanese pedigrees with Leber's hereditary optic neuropathy]

Although point mutation at nucleotide position 11778 of mitochondrial (mt) DNA is associated with Leber's hereditary optic neuropathy (LHON), the existence of the mutation alone is not sufficient for LHON expression. Whether the mutation is homo- or heteroplasmic, or whether secondary mutations additionally exist did not explain intra- or interfamilial phenotypic variations in at least 10 Japanese pedigrees tested. Segregation analysis showed that both mtDNA mutation and abnormal X-linked gene (XLG) are necessary for development of optic atrophy, and that an unfortunate X-inactivation is involved. The frequency of the presumed abnormal XLG and its penetrance are estimated to be about 0.1 and 0.2, respectively. The latter value is about twice as high as the value for Caucasian pedigrees. This evidence suggests a relatively homogeneous mtDNA abnormality and a low disease threshold derived from the XLG abnormality in female offsprings in Japanese LHON maternal lines.