Journal
NEUROMUSCULAR DISORDERS
Volume 23, Issue 3, Pages 269-276Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nmd.2012.12.010
Keywords
Chaperone-assisted selective autophagy (CASA); DnaJ homolog; Subfamily B; Member 6 (DNAJB6); Heat shock protein (HSP); Protein aggregation; Limb-girdle muscular dystrophy type 1D (LGMD1D)
Categories
Funding
- Research on Psychiatric and Neurological Diseases and Mental Health
- Research on Measures for Intractable Diseases
- Health Labour Sciences Research Grant for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare [20B-12, 20B-13]
- NCNP [23-4, 23-5, 23-6]
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DNAJB6, which encodes DnaJ homolog, subfamily B, member 6 (DNAJB6) was recently identified as a causative gene for limb-girdle muscular dystrophy type 1D (LGMD1D). DNAJB6 is a member of heat shock protein 40 and contains a J domain, G/F domain and C-terminal domain. Only three different mutations have been identified in 11 families. In this study, we identified seven Japanese individuals from four unrelated families who carried a DNATB6 mutation. We found a novel p.Phe96Ile substitution and a previously reported p.Phe96Leu change in the G/F domain of DNAJB6. All affected individuals showed slowly progressive muscle weakness, mainly in their legs, and their muscle pathology showed cytoplasmic inclusions and rimmed vacuoles. Our immunohistochemical analysis detected cytoplasmic accumulations associated with chaperone-assisted selective autophagy together with intranuclear accumulations of DNAJB6 and heat shock 22-kD protein 8 (HSPB8). This is the first report of Asian patients with LGMD1D. Our new findings may contribute to understanding the pathological mechanisms of this myopathy. (C) 2013 Elsevier B.V. All rights reserved.
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