Selcen Duygu
Department of Neurology, Division of Child Neurology and Neuromuscular Research Laboratory, Mayo Clinic, College of Medicine Rochester, Minnesota, USA.
Curr Opin Neurol. 2008 Oct;21(5):585-9. doi: 10.1097/WCO.0b013e32830a752b.
The aim of this communication is to provide an up-to-date overview of myofibrillar myopathies.
The most important recent advance in the myofibrillar myopathies has been the discovery that mutations in Z band alternatively spliced PDZ-containing protein and filamin C, as well as in desmin, alphaB-crystallin and myotilin, result in similar pathologic alterations in skeletal muscle that are typical of myofibrillar myopathy. Despite the increasing genetic heterogeneity, the clinical and morphologic phenotypes are remarkably homogeneous. The typical clinical manifestation is slowly progressive proximal, distal or both proximal and distal limb muscle weakness. Cardiomyopathy can be associated and is sometimes the presenting finding. Peripheral neuropathy also occurs in some patients. In every myofibrillar myopathy, there is abnormal accumulation of an array of proteins at ectopic sites as well as accumulation of degraded myofibrillar proteins forming large aggregates. The key issue now is to analyze the molecular mechanisms underlying the cascade of events that destroy the myofibrillar architecture and trigger the aberrant expression of multiple proteins.
Several disease genes have recently been recognized in myofibrillar myopathies. So far, the disease proteins identified are components of or chaperone for the Z-disk. In each case, the molecular defect leads to a stereotyped cascade of structural events in the muscle fiber.
本交流旨在提供肌原纤维肌病的最新概述。
肌原纤维肌病最近最重要的进展是发现Z带交替剪接含PDZ蛋白、细丝蛋白C以及结蛋白、αB晶状体蛋白和肌联蛋白中的突变，会导致骨骼肌出现典型的肌原纤维肌病病理改变。尽管遗传异质性增加，但临床和形态学表型却非常一致。典型临床表现为缓慢进展的近端、远端或近端和远端肢体肌肉无力。可伴有心肌病，有时是首发表现。部分患者还会出现周围神经病变。在每种肌原纤维肌病中，一系列蛋白质在异位部位异常积聚，以及降解的肌原纤维蛋白积聚形成大聚集体。现在的关键问题是分析破坏肌原纤维结构并触发多种蛋白质异常表达的一系列事件背后的分子机制。
最近在肌原纤维肌病中发现了几个致病基因。到目前为止，已鉴定出的致病蛋白是Z盘的组成成分或伴侣蛋白。在每种情况下，分子缺陷都会导致肌纤维中一系列固定的结构事件。
