A dysfunctional desmin mutation in a patient with severe generalized myopathy
A dysfunctional desmin mutation in a patient with severe generalized myopathy
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DOI：
10.1073/pnas.95.19.11312
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发表时间：
1998-09-15
影响因子：
11.1
通讯作者：
Fuchs, E
中科院分区：
文献类型：
--
作者：
Muñoz-Mármol, AM;Strasser, G;Fuchs, E
缺乏结蛋白的小鼠会产生具有 Z 盘和正常肌节组织的肌纤维。然而，肌肉在机械上很脆弱，并且在反复收缩时会退化。我们在此报告一名患有严重全身性肌病和结蛋白中间丝异常肌浆内积聚的人类患者。该患者的肌肉组织缺乏野生型结蛋白等位基因，并且具有编码蛋白质卷曲螺旋片段内 7-aa 缺失的结蛋白基因突变。我们表明，含有这种缺失的重组结蛋白不能在培养细胞中形成适当的结蛋白中间丝网络，也不能在体外组装成10-nm丝。这些发现提供了直接证据，表明结蛋白突变可导致人类肌病。
Mice lacking desmin produce muscle fibers with Z disks and normal sarcomeric organization. However, the muscles are mechanically fragile and degenerate upon repeated contractions. We report here a human patient with severe generalized myopathy and aberrant intrasarcoplasmic accumulation of desmin intermediate filaments. Muscle tissue from this patient lacks the wild-type desmin allele and has a desmin gene mutation encoding a 7-aa deletion within the coiled-coil segment of the protein. We show that recombinant desmin harboring this deletion cannot form proper desmin intermediate filament networks in cultured cells, nor is it able to assemble into IO-nm filaments in vitro. These findings provide direct evidence that a mutation in desmin can cause human myopathies.