Tsao C Y, Mendell J R
Department of Neurology, The Ohio State University, Columbus 43210, USA.
Semin Neurol. 1999;19(1):9-23. doi: 10.1055/s-2008-1040822.
New discoveries have dramatically changed the way we approach and think about patients with childhood muscular dystrophies. An aura of order and organization seems to be at hand for a group of diseases which previously seemed endlessly heterogeneous. We have learned that young boys and girls with proximal muscle weakness, large calves and elevated serum CK may have any one of a number of closely connected disorders which affect a complex of interacting proteins of the dystrophin-glycoprotein complex. This complex links the intracellular cytoskeleton to the extracellular matrix. Patients with Duchenne and Becker dystrophies lack dystrophin, while some of the limb girdle muscular dystrophies (an archaic term) are deficient in sarcoglycans and other proteins. The concept of interrelated disorders extends to the previously orphaned distal muscular dystrophies, or distal myopathies, as they are often called. A surprise finding is that the C. elegans protein, dysferlin, is conserved and expressed in man. We know little of the function of this protein in human primates, but its loss in muscle has brought seemingly disparate disorders together, since both a form of LGMD (2B) and distal myopathy (Miyoshi myopathy) are deficient in this same gene product. The congenital muscular dystrophies are also well-entrenched in our expanding concepts of orderliness of disease. The defect in the laminin-alpha2 chain, a direct ligand to the dystrophin-glycoprotein complex, causes a form of muscular dystrophy which affects infants. Another variant of congenital muscular dystrophy is deficient the integrin alpha7, an important laminin receptor. Finally, in Fukuyama congenital muscular dystrophy, the deficient fukutin gene product may also be linked to the basal lamina, permitting overmigration of neuronal cells which lead to micropolygyria in the brain, and at the same time cause basal lamina defects in the extracellular matrix of skeletal muscle, which leads to muscular dystrophy. As we approach the millennium, those of us who have seen the transition from the pre-molecular to the molecular era of myology know that we leave behind a great legacy of chaos (no great loss), replaced by a foundation for conceptual organization which will serve to establish new roots for research as well as for the enriched practice of medicine. The future looks bright for our field and our patients!
新的发现极大地改变了我们诊治和思考儿童肌营养不良症患者的方式。对于一类以前似乎无穷无尽、各不相同的疾病而言，一种有序和条理的氛围似乎即将到来。我们了解到，患有近端肌无力、小腿粗壮且血清肌酸激酶升高的年轻男孩和女孩，可能患有多种紧密相关的疾病中的任何一种，这些疾病会影响肌营养不良蛋白 - 糖蛋白复合物中的一组相互作用蛋白。这个复合物将细胞内的细胞骨架与细胞外基质连接起来。杜氏和贝克型肌营养不良症患者缺乏肌营养不良蛋白，而一些肢带型肌营养不良症（一个过时的术语）则缺乏肌聚糖和其他蛋白质。相关疾病的概念也扩展到了以前被视为罕见病的远端肌营养不良症，或者如人们通常所称的远端肌病。一个惊人的发现是，秀丽隐杆线虫的蛋白质——肌膜蛋白，在人类中是保守且有表达的。我们对这种蛋白质在人类灵长类动物中的功能知之甚少，但它在肌肉中的缺失却将看似不同的疾病联系在了一起，因为肢带型肌营养不良症（2B型）和远端肌病（三好肌病）这两种疾病都缺乏这种相同的基因产物。先天性肌营养不良症也在我们不断扩展的疾病有序性概念中占据了重要地位。层粘连蛋白α2链是肌营养不良蛋白 - 糖蛋白复合物的直接配体，其缺陷会导致一种影响婴儿的肌营养不良症。先天性肌营养不良症的另一个变体缺乏整合素α7，这是一种重要的层粘连蛋白受体。最后，在福山先天性肌营养不良症中，缺陷的福库汀基因产物可能也与基膜有关，它会导致神经元细胞过度迁移，进而在大脑中形成微小多脑回，同时在骨骼肌的细胞外基质中导致基膜缺陷，从而引发肌营养不良症。随着我们迈向千禧年，我们这些见证了从肌病学前分子时代到分子时代转变的人知道，我们摒弃了混乱的巨大遗留物（没什么大损失），取而代之的是一个概念性组织的基础，它将为研究以及医学实践的丰富发展建立新的根基。我们这个领域以及我们的患者的未来看起来一片光明！
