Multicenter study on the frequency of three primary mutations of mitochondrial DNA in Japanese pedigrees with Leber’s hereditary optic neuropathy: comparison with American and British counterparts

Abstract

We retrospectively evaluated the incidence and clinical characteristics of three primary mutations in mitochondrial DNA at nucleotide positions (np) 3460, 11778, and 14484 in 142 Japanese patients (125 families) with Leber’s hereditary optic neuropathy (LHON). Data was collected on LHON patients at four institutions in Japan. Mutations were identified at np 3460 in 5/125 (4%) families, at np 11778 in 114/125 (91%) families, and at np 14484 in 6/125 (5%) families. Thus, Japanese patients with LHON exhibited a high incidence of the 11778 primary mutation. Except for a family history of optic atrophy, the clinical features of Japanese patients with these three mutations were similar to those reported for 114 patients (75 families) in the USA and 112 patients (79 families) in the UK, despite their different mtDNA backgrounds. The final visual outcome was better in the Japanese patients with the 3460 or 14484 mutation than the 11778 mutation. The proportion of Japanese patients with either the 3460 (20%) or the 14484 (33%) mutation and a family history of optic atrophy was lower than that reported in either American or British patients with LHON.