title: [Study of a Bethlem myopathy pedigree resulted from a novel mutation of COL6A3 gene].
abstract: OBJECTIVE
  To determine the molecular etiology for a muscular dystrophy pedigree with target region sequencing platform using hereditary myopathy capture array.
  
  
  METHODS
  Specific gene testing was performed based on the clinical diagnosis. Since no pathogenic mutation was found, target region sequencing with hereditary myopathy capture array combined with Sanger sequencing and bioinformatics analysis were employed in turn. PolyPhen and NCBI were used to evaluate the pathogenicity of identified mutation and conservation of the gene.
  
  
  RESULTS
  Target region sequencing indicated the proband has carried a heterozygous c.3353 A>C mutation of COL6A3 gene, which was confirmed by Sanger-sequencing in 4 affected individuals from the family. The same mutation was not detected in healthy members of the pedigree. Bioinformatics analysis suggested that the mutation has caused a highly pathogenic amino acid substitution from Histidine to Proline. The affected patients featured normal intelligence with mild myogenic damage by muscle biopsy, slightly increased serum creatine kinase and slow disease progression, which was consistent with Bethlem myopathy.
  
  
  CONCLUSIONS
  Target region sequencing is an effective and efficient method for genetic testing. The heterozygous c.3353A>C mutation in exon 8 of the COL6A3 gene probably underlies the Bethlem myopathy with autosomal dominant inheritance.
authors.affiliation: Institute of Reproduction and Stem Cell Engineering, Central South University, Changsha, Hunan 410078, P. R. China. tanyueqiu@csu.edu.cn.
authors.forename: Wanglong
authors.initials: W
authors.lastname: Cao
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Changgao
authors.initials: C
authors.lastname: Zhong
authors.forename: Guangxiu
authors.initials: G
authors.lastname: Lu
authors.forename: Yueqiu
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D024142:Collagen Type VI / Q000235:genetics*; D003286:Contracture / Q000235:genetics*; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics; D020125:Mutation, Missense; D010375:Pedigree; D055815:Young Adult
chemical_list: D024142:Collagen Type VI