DNAJB6 myopathy in an Asian cohort and cytoplasmic/nuclear inclusions
DNAJB6 myopathy in an Asian cohort and cytoplasmic/nuclear inclusions
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DOI：
10.1016/j.nmd.2012.12.010
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发表时间：
2013-03-01
影响因子：
2.8
通讯作者：
Nishino, Ichizo
中科院分区：
文献类型：
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作者：
Sato, Takatoshi;Hayashi, Yukiko K.;Nishino, Ichizo
DNAJB6编码DNAJ同源物，B亚家族，成员6(DNAJB6)，最近被发现是肢体带状肌营养不良1D(LGMD1D)的致病基因。DNAJB6是热休克蛋白40的成员，含有J结构域、G/F结构域和C末端结构域。在11个家系中只发现了三种不同的突变。在这项研究中，我们确定了来自四个无关家庭的七名日本人携带DNatB6突变。我们在DNAJB6的G/F结构域发现了一个新的p.Phe96Ile替换和一个先前报道的p.Phe96Leu改变。所有受影响的人都表现出缓慢进行性的肌肉无力，主要是在他们的腿部，他们的肌肉病理表现为细胞质内含物和有边框的空泡。我们的免疫组织化学分析检测到与伴侣辅助的选择性自噬相关的细胞质积累以及DNAJB6和热休克22-kD蛋白8(HSPB8)的核内积累。这是首例亚洲LGMD1D患者的报告。我们的新发现可能有助于理解这种肌病的病理机制。(C)2013爱思唯尔B.V.保留所有权利。
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.