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

作者：Pei‐Chien Tsai, Yuh‐Show Tsai, Bing‐Wen Soong, Yi‐Hsiang Huang, Hao‐Hua Wu, Y.‐H. Chen, Kuang-Hui Lin, Yi‐Chu Liao, Yi‐Chung Lee · 发表于：Clinical Genetics · 年份：2017 · DOI：10.1111/cge.13001 · 被引用次数：23 · 研究领域：Muscle Physiology and Disorders、Cardiomyopathy and Myosin Studies、Nuclear Structure and Function

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.