Molecular Genetic Study on Primary and Secondary Mitochondrial DNA Mutations of Leber's Hereditary Optic Neuropathy in Koreans

ABSTRACT

PURPOSE: In order to evaluate the spectrum of mitochondrial DNA (mtDNA) mutations in the patients with suspected Leber's hereditary optic neuropathy (LHON). METHODS: We investigated 14 primary mtDNA mutations at nucleotide positions (nps 3460A, 4160C, 5244A, 9101C, 9804A, 10663C, 11778A, 13730A, 14459A, 14482G, 14484C, 14495G, 14498T, and 14568T) and one common secondary mutation (np15257A) in 82 Korean patients with suspected LHON. RESULTS: Among them, only three kinds of LHON mutations were identified in 60 (73%) of 82 probands, which were comprised of 46 (56%) cases with the 11778A, 13 (16%) with the 14484C, and 1 (1%) with the 3460A. None of the other mtDNA mutations was detected. Of the 60 probands with LHON positive mutations, 19 (32%) had relevant family histories. Heteroplasmy was determined in 2 (4%) of the 46 probands with the 11778A and 1 (8%) of 13 probands with the 14484C. CONCLUSIONS: In conclusion, the 11778A was the most common cause (56%), and higher prevalence of the 14484C and the lower prevalence of the 3460A were characteristic in Korean patients with LHON. Especially, the 3460A had a remarkable racial difference compared with Caucasians. Except 3460A, 11778A, and 14484C, the other mutations screened may not be involved in pathogenesis and not have a synergistic effect on the clinical expression of LHON in Koreans.