Genetic and clinical characteristics of Japanese patients with Leber's hereditary optic neuropathy

摘要

Objective To clarify characteristics of Japanese patients with Leber's hereditary optic neuropathy (LHON). Methods One hundred and twenty five families with LHON confirmed by molecular analysis were examined genetically and clinically. Results Primary mtDNA mutations were identified in 125 Japanese families at np3460 in 5 (4%) families, npll778 in114 (91%) families, and npl4484 in 6 (5%) families. The prevalence of the Japanese patients with the 11778 mutation ishigher than that of the Caucasians. The final visual outcome was better in the patients with the 3460 or 14484 mutationthan the 11778 mutation. The proportion of family history of optic atrophy in Japanese patients with the 3460 (20%) or14484 mutation (33%) was lower than that reported in either American or British patients with LHON. Haplotype analysisof Japanese LHON patients revealed that the 11778 mutation was associated with mtDNA haplogroup M (38%) and the 14484 mutation with mtDNA haplogroup M (57%): 29% of normal subjects was associated with haplogroup M. The study of relationship between the final visual acuities and the worst visual acuities revealed that 73% (8 out of 11) of eyes withthe worst visual acuities between 0.07 to 0.1 recovered their vision over 0.3. On the other hand, 93% (25 out of 27) of eyeswith the worst visual acuities below 0.01 showed no recovery over 0.05. The characteristic of visual recovery pattern isfenestrated central scotoma. Conclusions Haplotype of Japanese LHON is associated with Asian specific mtDNA haplogroup M, and the prevalence of the patients with the 11778 mutation is high. Clinical features of Japanese LHON patients with the three mutations were almost the same as those of Caucasian patients despite different genetic background. References 1. Mashima Y, et al. Spectrum of pathologic mitochondrial DNA mutation and clinical features in Japanese families with Leber's hereditary optic neuropathy. Curr Eye Res 16:403-408, 1998. 2.Yamada K, et al. 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. Neuro-ophthalmol 22:187-193, 1999. 3.Sudoyo H, et al. Asian-specific mtDNA backgrounds associated with the primary G11778 A mutation of Leber's hereditary optic neuropathy.