2. Academic Validation
  3. A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy and compromises DNAJB6 function

A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy and compromises DNAJB6 function

  • Clin Genet. 2017 Aug;92(2):150-157. doi: 10.1111/cge.13001.
P-C Tsai 1 2 3,  Y-S Tsai 4,  B-W Soong 1 2 3,  Y-H Huang 4 5,  H-T Wu 6 7,  Y-H Chen 1 2,  K-P Lin 1 2,  Y-C Liao 1 2,  Y-C Lee 1 2 3
Affiliations

Affiliations

  • 1 Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.
  • 2 Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
  • 3 Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
  • 4 Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
  • 5 Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
  • 6 Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.
  • 7 Department of Radiology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
PMID: 28233300 DOI: 10.1111/cge.13001
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.

Materials and 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.

Conclusion: This study expands the molecular spectrum of DNAJB6 mutations and also emphasizes the pathogenic role of DNAJB6 dysfunction in distal-onset myopathy.

Keywords

DNAJB6; LGMD; distal-onset myopathy; exome sequencing; limb-girdle muscular dystrophy; myopathy.

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