Pegoraro E, Mancias P, Swerdlow S H, Raikow R B, Garcia C, Marks H, Crawford T, Carver V, Di Cianno B, Hoffman E P
Department of Molecular Genetics, University of Pittsburgh, School of Medicine, PA 15261, USA.
Ann Neurol. 1996 Nov;40(5):782-91. doi: 10.1002/ana.410400515.
Ten laminin alpha2-deficient patients were identified by both immunofluorescence and immunoblotting (30% of congenital muscular dystrophy patients tested). Three of the laminin alpha2-deficient patients were carrying a diagnosis 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 alpha2-coding sequence was screened for causative mutations by reverse transcriptase-polymerase chain reaction/single-stranded conformational polymorphism analysis in muscle biopsy 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 histopathology in this patient showed a striking inflammatory infiltrate of T cells and B cells. Reexamination of biopsy specimens from other laminin alpha2-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 subset of congenital muscular dystrophy is proposed. Our data show that muscle histopathology showing a neonatal inflammatory process should be considered consistent with congenital muscular dystrophy.
通过免疫荧光和免疫印迹法鉴定出10例层粘连蛋白α2缺陷患者（占所检测先天性肌营养不良患者的30%）。在免疫染色研究之前，其中3例层粘连蛋白α2缺陷患者被诊断为婴儿型多发性肌炎。10例merosin缺陷患者的临床特征具有同质性，出生时严重松软，运动发育里程碑延迟，磁共振成像显示白质改变但智力正常。通过逆转录聚合酶链反应/单链构象多态性分析，对5例患者肌肉活检标本中的10 kb层粘连蛋白α2编码序列进行致病突变筛查，随后对异常构象体进行自动测序。在1例患者的两个等位基因中均发现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细胞显著炎性浸润。重新检查其他层粘连蛋白α2缺陷患者的活检标本，发现每例均有轻微炎症迹象。基于这些发现以及提示肌肉再生失败的组织学和临床情况，提出了这种主要类型先天性肌营养不良的发病机制模型。我们的数据表明，显示新生儿炎症过程的肌肉组织病理学应被视为与先天性肌营养不良一致。
