Dalakas Marinos C, Dagvadorj Ayush, Goudeau Bertrand, Park Kye-Yoon, Takeda Kazuyo, Simon-Casteras Monique, Vasconcelos Olavo, Sambuughin Nyamkhishig, Shatunov Alexey, Nagle James W, Sivakumar Kumaraswamy, Vicart Patrick, Goldfarb Lev G
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 4B37, 10 Central Drive, MSC 1361, Bethesda, MD 20892, USA.
Neuromuscul Disord. 2003 Mar;13(3):252-8. doi: 10.1016/s0960-8966(02)00271-7.
Desmin myopathy is a familial or sporadic disorder characterized by the presence of desmin mutations that cause skeletal muscle weakness associated with cardiac conduction block, arrhythmia and heart failure. Distinctive histopathologic features include intracytoplasmic accumulation of desmin-reactive deposits and electron-dense granular aggregates in skeletal and cardiac muscle cells. We describe two families with features of adult-onset slowly progressive skeletal myopathy without cardiomyopathy. N342D point mutation was present in the desmin helical rod domain in patients of family 1, and I451M mutation was found in the non-helical tail domain in patients of family 2. Of interest, the same I451M mutation has previously been reported in patients with cardiomyopathy and no signs of skeletal myopathy. Some carriers of the I451M mutation did not develop any disease, suggesting incomplete penetrance. Expression studies demonstrated inability of the N342D mutant desmin to form cellular filamentous network, confirming the pathogenic role of this mutation, but the network was not affected by the tail-domain I451M mutation. Progressive skeletal myopathy is a rare phenotypic variant of desmin myopathy allelic to the more frequent cardio-skeletal form.
结蛋白肌病是一种家族性或散发性疾病，其特征是存在结蛋白突变，这些突变会导致骨骼肌无力，并伴有心脏传导阻滞、心律失常和心力衰竭。独特的组织病理学特征包括骨骼肌和心肌细胞中结蛋白反应性沉积物的胞浆内积聚以及电子致密颗粒聚集体。我们描述了两个具有成人起病的缓慢进展性骨骼肌病特征且无心肌病的家系。家系1的患者在结蛋白螺旋杆结构域存在N342D点突变，家系2的患者在非螺旋尾部结构域发现了I451M突变。有趣的是，先前在患有心肌病且无骨骼肌病迹象的患者中报道过相同的I451M突变。一些I451M突变携带者未患任何疾病，提示存在不完全外显。表达研究表明，N342D突变型结蛋白无法形成细胞丝状网络，证实了该突变的致病作用，但该网络不受尾部结构域I451M突变的影响。进行性骨骼肌病是结蛋白肌病的一种罕见表型变异，与更常见的心脏-骨骼肌型等位基因。
