title: A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy and compromises DNAJB6 function.
abstract: BACKGROUND
  Mutations in the DNAJB6 gene have been identified as a rare cause of dominantly inherited limb-girdle muscular dystrophy or distal-onset myopathy.
  
  
  METHODS
  Exome sequencing was performed to investigate a Taiwanese family with a dominantly inherited distal-onset myopathy. Functional effects of the causal mutation were investigated in vitro.
  
  
  RESULTS
  Exome sequencing of the two affected individuals in this family identified a heterozygous mutation, c.287C>T (p.Pro96Leu) in the DNAJB6 gene, which co-segregated with the myopathy within all 12 family members. Notably, this mutation is novel and localizes within the glycine and phenylalanine-rich (G/F) domain and alters an amino acid residue previously reported with a different mutation. Furthermore, immunofluorescence analyses and filter trap assay demonstrated that the c.287C>T (p.Pro96Leu) mutation possessed a dominant negative effect on the anti-aggregation function of DNAJB6 protein.
  
  
  CONCLUSIONS
  This study expands the molecular spectrum of DNAJB6 mutations and also emphasizes the pathogenic role of DNAJB6 dysfunction in distal-onset myopathy.
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: P-C
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Y-S
authors.initials: YS
authors.lastname: Tsai
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: B-W
authors.initials: BW
authors.lastname: Soong
authors.affiliation: Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.|Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Radiology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: H-T
authors.initials: HT
authors.lastname: Wu
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: K-P
authors.initials: KP
authors.lastname: Lin
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Liao
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Y-C
authors.identifier: http://orcid.org/0000-0003-0102-164X
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000328:Adult; D017668:Age of Onset; D049310:Distal Myopathies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics*; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000503:physiopathology; D009154:Mutation; D020125:Mutation, Missense / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000073359:Exome Sequencing
chemical_list: C485565:DNAJB6 protein, human; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins
keywords: DNAJB6; LGMD; distal-onset myopathy; exome sequencing; limb-girdle muscular dystrophy; myopathy