title: [c.2381-3T>C mutation of DMD gene: a rare SNP without significant pathogenicity].
abstract: OBJECTIVE
  To clarify the nature of a DMD splice acceptor mutation c.2381-3T>C.
  
  
  METHODS
  Genomic DNA was extracted from 5 members of a family affected with DMD. For an obligatory carrier, after excluding gross deletion and duplication of the DMD gene with multiplex ligation-dependent probe amplification (MLPA) method, all coding and splice site sequences of the DMD gene were analyzed with Next Generation Sequencing followed by confirmation with targeted Sanger sequencing. Mutations of the carrier were detected in other 4 members. For the splice site mutation, mini-gene was constructed and expressed in vitro to detect the number of transcript and cDNA sequence.
  
  
  RESULTS
  A known nonsense mutation (c.8038C>T, p.Arg2680Ter) was identified in the carrier, her sister and the mother. The rest 4 members, except for the mother from the first generation, have all carried the c.2381-3T>C mutation. The latter has been described as a splice site mutation to cause DMD. One of 135 male adults without DMD was also detected to have carried the c.2381-3T>C mutation. No additional transcript was produced by the mini-genes containing c.2381-3T>C mutation.
  
  
  CONCLUSIONS
  The c.8038C>T（p.Arg2680Ter）mutation of DMD gene probably underlies the disease in this family. The presence of the c.2381-3T>C mutation in a asymptomatic male and a non-DMD male control, together with the normal in vitro expression of the mini-gene carrying the c.2381-3T>C, strongly suggested that the c.2381-3T>C mutation collected in the Human Gene Mutation Database is a rare SNP without significant pathogenicity.
authors: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China. Email: yangyuan@scu.edu.cn.
authors: Yuanlong
authors: Y
authors: Yan
authors: Yuan
authors: Y
authors: Yang
mesh_terms: D016189:Dystrophin / Q000235:genetics*; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: C484258:DMD protein, human; D016189:Dystrophin