Congenital muscular dystrophy with primary laminin alpha2 (merosin) deficiency presenting as inflammatory myopathy.
Congenital muscular dystrophy with primary laminin alpha2 (merosin) deficiency presenting as inflammatory myopathy.
复制标题
先天性肌营养不良症伴原发性层粘连蛋白 α2（merosin）缺乏，表现为炎症性肌病。
DOI：
10.1002/ana.410400515
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发表时间：
1996
影响因子：
11.2
通讯作者：
Hoffman,EP
中科院分区：
文献类型：
--
作者：
Pegoraro,E;Mancias,P;Swerdlow,SH;Raikow,RB;Garcia,C;Marks,H;Crawford,T;Carver,V;DiCianno,B;Hoffman,EP
通过免疫荧光和免疫印迹鉴定了 10 名层粘连蛋白 α2 缺陷患者（测试了 30% 的先天性肌营养不良症患者）。在免疫染色研究之前，三名层粘连蛋白 α2 缺陷患者被诊断为婴儿多发性肌炎。 10 名 merosin 缺陷患者的临床特征是一致的，出生时严重软弱，运动里程碑的实现延迟，磁共振成像显示白质变化，但智力正常。通过逆转录酶聚合酶链反应/单链构象多态性分析对 5 名患者的肌肉活检标本筛选 10 kb 层粘连蛋白 α2 编码序列的致病突变，然后对异常构象异构体进行自动测序。在 1 名患者的两个等位基因中发现了明显的功能丧失性缺失突变。该患者的肌肉组织病理学显示 T 细胞和 B 细胞明显炎症浸润。对其他层粘连蛋白 α2 缺陷患者的活检标本进行重新检查，均显示出轻微的炎症迹象。基于这些发现以及表明肌肉再生失败的组织学和临床图片，提出了先天性肌营养不良症这一主要亚型的发病机制模型。我们的数据表明，肌肉组织病理学显示新生儿炎症过程应被认为与先天性肌营养不良症一致。
Ten laminin α2‐deficient patients were identified by both immunofluorescence and immunoblotting (30% of congenital muscular dystrophy patients tested). Three of the laminin α2‐deficient patients were carrying a diagnonsis of infantile polymyositis prior to immunostaining studies. The clinical features in the 10 merosin‐deficient patients were homogeneous, with severe floppiness at birth, delay in achievement of motor milestones, and magnetic resonance imaging findings of white matter changes with normal intelligence. The 10‐kb laminin α2‐coding sequence was screened for causative mutations by reverse transcriptase‐polymerase chain reaction/single‐stranded confronmational polymorphism analysis in muscle biopys specimens from 5 patients, followed by automatic sequencing of aberrant conformers. Clear loss‐of‐function deletion mutations were identified in both alleles of 1 patient. Muscle histopahtology in this patient showed a striking inflammatory infiltrate of T cells and B cells. REexaminatin of biopys specimens from other laminin α2‐deficient patients showed minor signs of inflammation in each. Based on these findings and the histological and clinical picture suggesting failure of muscle regeneration, a pathogenesis model for this major subswt of congenital muscular dystrophy is proposed. Our data show that muscle histopatholgoy showing a neonatal inflammatory process shold be considered consistent with congenital muscular dystrophy.