A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy and compromises DNAJB6 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.
['Tsai|P-C|PC|', 'Tsai|Y-S|YS|', 'Soong|B-W|BW|', 'Huang|Y-H|YH|', 'Wu|H-T|HT|', 'Chen|Y-H|YH|', 'Lin|K-P|KP|', 'Liao|Y-C|YC|', 'Lee|Y-C|YC|http://orcid.org/0000-0003-0102-164X']
D000328:Adult D017668:Age of Onset D049310:Distal Myopathies D005260:Female D020022:Genetic Predisposition to Disease D050956:HSP40 Heat-Shock Proteins D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D018832:Molecular Chaperones D018482:Muscle, Skeletal D009154:Mutation D020125:Mutation, Missense D009419:Nerve Tissue Proteins D000073359:Whole Exome Sequencing
DNAJB6 distal-onset myopathy myopathy limb-girdle muscular dystrophy exome sequencing LGMD