Mutational and clinical spectrum in Korean with Leber’s hereditary optic neuropathy

Purpose To investigate the spectrum of mutations of mitochondrial DNA (mtDNA) and clinical features in Korean with Leber’s hereditary optic neuropathy (LHON). Methods Total genomic DNA was isolated from the peripheral blood leukocytes of the patients who were suspicious of LHON. The presence of mutations were screened by direct sequencing were analyzed against mitochondrial reference sequence on genetic analyzer. The ophthalmologic examinations of patients were conducted, including visual acuity(VA), color vision, retinal nerve fiber layer(RNFL) thickness and visual field(VF). Results Two primary mutations (G1778A, T14484C) and five secondary mutations (T3394C, C3497T, G11696A, A11392C, T14502C) were detected in 34 of 164 unrelated patients. Among the 34 patients, primary mutation was detected in 21 patients, secondary mutation in 11 patients, and combined primary and secondary mutation in 2 patients. Compared the patients with primary mutation, patients with secondary mutation had increased proportion of woman. The VA was significantly better in secondary mutation than primary mutation. Also, the severity of the color vision deficiency was significantly mild in secondary mutation relative to primary mutation. No significant difference was found in the OCT parameters between the groups including temporal area. However, the visual field index and mean deviation of the visual field test were different significantly between groups. Conclusion Our results emphasize the possible heterogeneity of LHON-associated mtDNA mutations and clinical phenotypes in Korean LHON patients. Candidate pathogenic mtDNA mutations including major primary mutations should be rigorously investigated.