DNAJB6 myopathy in an Asian cohort and cytoplasmic/nuclear inclusions.

Takatoshi Sato, Yukiko K Hayashi, Yasushi Oya, Tomoyoshi Kondo, Kazuma Sugie, Daita Kaneda, Hideki Houzen, Ichiro Yabe, Hidenao Sasaki, Satoru Noguchi, Ikuya Nonaka, Makiko Osawa, Ichizo Nishino

Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan.

Neuromuscular disorders : NMD 2013 Mar

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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 DNAJB6 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. Copyright © 2013 Elsevier B.V. All rights reserved.

Citation

Takatoshi Sato, Yukiko K Hayashi, Yasushi Oya, Tomoyoshi Kondo, Kazuma Sugie, Daita Kaneda, Hideki Houzen, Ichiro Yabe, Hidenao Sasaki, Satoru Noguchi, Ikuya Nonaka, Makiko Osawa, Ichizo Nishino. DNAJB6 myopathy in an Asian cohort and cytoplasmic/nuclear inclusions. Neuromuscular disorders : NMD. 2013 Mar;23(3):269-76