P-C Tsai1,2,3, Y-S Tsai4, B-W Soong1,2,3, Y-H Huang4,5, H-T Wu6,7, Y-H Chen1,2, K-P Lin1,2, Y-C Liao1,2, Y-C Lee1,2,3. 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.
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.
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.
Authors: Christina Zarouchlioti; David A Parfitt; Wenwen Li; Lauren M Gittings; Michael E Cheetham Journal: Philos Trans R Soc Lond B Biol Sci Date: 2018-01-19 Impact factor: 6.237
Authors: Saeed A Bohlega; Sarah Alfawaz; Hussam Abou-Al-Shaar; Hindi N Al-Hindi; Hatem N Murad; Mohamed S Bohlega; Brian F Meyer; Dorota Monies Journal: Acta Myol Date: 2018-09-01