A novel DNAJB6 mutation causes dominantly inherited distal‐onset myopathy and compromises DNAJB6 function. Issue 2 (12th April 2017)

• Record Type: Journal Article
• Authors: Tsai, P.‐C.; Tsai, Y.‐S.; Soong, B.‐W.; Huang, Y.‐H.; Wu, H.‐T.; Chen, Y.‐H.; Lin, K.‐P.; Liao, Y.‐C.; Lee, Y.‐C.
• Is Part Of: Clinical genetics. Volume 92:Issue 2(2017)
• Page Start: 150
• Page End: 157
• Publication Date: 2017-04-12
• Subjects: distal‐onset myopathy -- DNAJB6 -- exome sequencing -- LGMD -- limb‐girdle muscular dystrophy -- myopathy; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13001
• Languages: English
• ISSNs: 0009-9163

Abstract

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. Abstract :