SPECTRUM OF PATHOGENIC MITOCHONDRIAL-DNA MUTATIONS AND CLINICAL-FEATURES IN JAPANESE FAMILIES WITH LEBERS HEREDITARY OPTIC NEUROPATHY

Purpose. To investigate the incidence and clinical significance of pri mary or proposed secondary mitochondrial DNA (mtDNA) mutations in Japa nese patients with Leber's hereditary optic neuropathy (LHON). Methods . Blood samples from the 80 unrelated Japanese patients with bilateral optic atrophy were screened for primary LHON mutations. Patients foun d to have a primary LHON mutation were then tested for 9 proposed seco ndary LHON mutations. We investigated the association between these mu tations and clinical characteristics. Results. Primary mtDNA mutations were identified in 68 patients: at np 3460 in 3 (4%) of 68 patients, at np 11778 in 59 patients (87%), and at np 14484 in 6 patients (9%). We identified 5 secondary mtDNA mutations (at np 3394, 4216, 7444, 943 8 or 13708) in 10 (15%) of 68 LHON patients and 3 mutations (at np 339 4, 4216 or 3708) in 6 (7%) of 90 healthy Japanese individuals. No pati ent was positive for more than one secondary mutation. The frequency o f secondary mutations was similar in the 68 LHON patients and 90 contr ols. The clinical features of the Japanese patients with any of the 3 primary LHON mutations were similar to those of Caucasian patients, de spite different mtDNA backgrounds in these populations. The percentage of patients with familial LHON harboring the 3460 or 14484 mutations was lower in the Japanese population. Conclusions. Japanese patients w ith LHON exhibited a very high incidence (87%) of the 11778 primary mu tation. Most of the proposed secondary LHON mutations were rare in the Japanese population and they, except the 7444 mutation, may not influ ence the clinical features of LHON.