Massive muscle cell degeneration in the early stage of merosin-deficient congenital muscular dystrophy
Massive muscle cell degeneration in the early stage of merosin-deficient congenital muscular dystrophy
复制标题
DOI：
10.1016/s0960-8966(00)00203-0
复制
发表时间：
2001-05-01
影响因子：
2.8
通讯作者：
Arahata, K
中科院分区：
文献类型：
--
作者：
Hayashi, YK;Tezak, Z;Arahata, K
原发性缺裂蛋白型先天性肌营养不良症（CMD）是一种严重的先天性肌肉疾病，由层粘连蛋白α 2链基因（LAMA 2）突变引起。该疾病的特征是在婴儿早期骨骼肌发生显著的营养不良性变化，而对肌纤维变性的病理过程知之甚少。这里.我们报告了10例原发性缺裂蛋白CMD患者的骨骼肌免疫组化分析，使用了一组骨骼肌蛋白、细胞坏死和凋亡的分子标记。在最年轻的患者（52天大的婴儿）中，发生了与C5-9补体膜攻击复合物（MAC）沉积相关的显著的大量肌细胞变性。大多数的MAC阳性肌纤维表现出严重紊乱的免疫反应，肌营养不良蛋白，肌营养不良蛋白聚糖，和其他肌膜蛋白。此外，我们还发现了散在的凋亡阳性信号，在另外6例小于1岁的患者中也观察到了类似但较轻的变化。在3岁以上的患者中，MAC和凋亡信号阳性的肌纤维几乎检测不到。这些发现意味着大量的肌纤维变性发生在非常早期的阶段，缺裂蛋白的CMD，并可能有助于从婴儿早期肌肉的严重营养不良的变化。(C)2001爱思唯尔科技有限公司。保留所有权利。
Primary merosin-deficient congenital muscular dystrophy (CMD) is a severe form of congenital muscular disorder which is caused by mutations in the laminin alpha2 chain gene (LAMA2). The disease is characterized by marked dystrophic changes in skeletal muscles during early infancy, while little is known about the pathological process of the muscle fiber degeneration. Here. we report the immunohistochemical analysis of skeletal muscle in ten patients with primary merosin-deficient CMD using a panel of molecular markers for skeletal muscle proteins, cellular necrosis, and apoptosis. In the youngest patient (a 52 day old baby), prominent massive muscle cell degeneration occurred in association with the deposition of the C5-9 complement membrane attack complex (MAC). Most of the MAC-positive muscle fibers showed a severely deranged immunoreaction to dystrophin, dystroglycans, and other sarcolemmal proteins. In addition, we found scattered positive signals for apoptosis, Similar but milder changes were also observed in six other patients younger than 1 year. In the patients older than 3 years, muscle fibers positive for MAC and apoptotic signals were barely detectable. These findings imply that massive muscle fiber degeneration occurs in the very early stage of merosin-deficient CMD and may contribute to the severe dystrophic changes in muscle from early infancy. (C) 2001 Elsevier Science B.V. All rights reserved.