| Summary: | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>We screened mutation m.10680G > A in the <it>MT-ND4L </it>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.</p> <p>Results</p> <p>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 <it>MT-ND1 </it>and <it>MT-ND5 </it>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) (<it>P </it>= 0.0005).</p> <p>Conclusion</p> <p>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.</p>
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