Frequency of mitochondrial DNA mutations in Japanese families with Leber's Hereditary Optic Neuropathy(LHON)

Purpose. Over 15 mtDNA nucleotide changes have been associated with LHON as primary or secondary mutations in Caucasian patients with LHON. The incidence of these mutations in Japanese families was investigated. Methods. Total DNA was extracted from blood in 120 patients with bilateral acute or subacute loss of vision, or optic atrophy. Five primary LHON mutations (the 3460, 9438, 9804, 11778, and 14484 mutations) were screened by the PCR/restriction enzyme assay. Then, eight secondary LHON mutations (the 3394, 4216, 4917, 5244, 7444, 13708, 15257 and 15812 mutations) were screened in patients with one of the primary LHON mutations. The mutations were confirmed by sequencing. Results. We have identified three primary mutations in 59 families; the 11778 mutation in 51 families, the 14484 mutation in 5 families and the 3460 mutation in 3 families. The three secondary mutations were identified in only 7 families; the 3394 mutation in 2 families with the 11778 and one family with the 14484 mutation, the 7444 mutation in one family with the 3460 mutation, and the 13708 mutation in 3 families with the 11778 mutation. Conclusions. The frequency of the 11778 mutations (51/59, 86%) in Japanese LHON is high compared with Caucasian families. However, proposed 8 secondary mutations are rare among Japanese LHON.