title: Mitochondrial DNA mutation m.10680G > A is associated with Leber hereditary optic neuropathy in Chinese patients.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors.forename: A-Mei
authors.initials: AM
authors.lastname: Zhang
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jia
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D044466:Asian People / Q000235:genetics*; D002138:Calibration; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005190:Family; D050259:Genes, Mitochondrial / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D054629:Genome, Mitochondrial / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000502:physiology; D029242:Optic Atrophy, Hereditary, Leber / Q000208:ethnology / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods / Q000592:standards; D020641:Polymorphism, Single Nucleotide / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial