mtDNA m.3635G>A may be classified as a common primary mutation for Leber hereditary optic neuropathy in the Chinese population

Leber hereditary optic neuropathy (LHON) is the most common cause of sudden blindness in young adults and is caused by mtDNA mutations. At least 30 mutations have been identified but only the three common mutations (m.3460G>A, m.11778G>A, and m.14484T>C) have been extensively studied. Most other mutations, including m.3635G>A, are considered as potential candidate LHON mutations due to a lack of enough evidence. The frequency of these potential candidate mutations in populations has not been determined. In this study, we performed a comprehensive survey of m.3635G>A in 1398 unrelated probands suspected to have LHON and detected the m.3635G>A mutation in 8 cases, including 4 probands with a family history of LHON. The mutation in 7 cases was homoplasmic, but the mutation in one patient was heteroplasmic. Patients with the m.3635G>A mutation demonstrated the typical phenotype of LHON. Our results provide strong evidence that similar to m.3460G>A, m.3635G>A is a pathogenic and common LHON mutation in the Chinese population.