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A novel DNAJB6 mutation causes dominantly inherited distal‐onset myopathy and compromises DNAJB6 function
Author(s) -
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.
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13001
Subject(s) - exome sequencing , mutation , genetics , myopathy , biology , limb girdle muscular dystrophy , muscular dystrophy , gene
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.