Mitochondrial DNA mutation m.10680G>A is associated with Leber hereditary optic neuropathy in Chinese patients (Journal of Translational Medicine)

Background: Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with gender biased and incomplete penetrance. The majority of LHON patients are caused by one of the three primary mutations (m.3460G>A, m.11778G>A and m.14484T>C). Rare pathogenic mutations have been occasionally reported in LHON patients. Methods: We screened mutation m.10680G>A in the MT-ND4L gene in 774 Chinese patients with clinical features of LHON but lacked the three primary mutations by using allele specific PCR (AS-PCR). Patients with m.10680G>A were further determined entire mtDNA genome sequence. Results: The optimal AS-PCR could detect as low as 10% heteroplasmy of mutation m.10680G>A. Two patients (Le1263 and Le1330) were identified to harbor m.10680G>A. Analysis of the complete mtDNA sequences of the probands suggested that they belonged to haplogroups B4a1 and D6a1. There was no other potentially pathogenic mutation, except for a few private yet reported variants in the MT-ND1 and MT-ND5 genes, in the two lineages. A search in reported mtDNA genome data set (n = 9277; excluding Chinese LHON patients) identified no individual with m.10680G>A. Frequency of m.10680G>A in Chinese LHON patients analyzed in this study and our previous studies (3/784) was significantly higher than that of the general populations (0/9277) (P = 0.0005). Conclusion: Taken together, we speculated that m.10680G>A may be a rare pathogenic mutation for LHON in Chinese. This mutation should be included in future clinical diagnosis.