Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Curr Neurol Neurosci Rep. 2012 Feb;12(1):92-101. doi: 10.1007/s11910-011-0234-7.
Congenital myasthenic syndromes (CMS) represent a heterogeneous group of disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Clinical, electrophysiologic, and morphologic studies have paved the way for detecting CMS-related mutations in proteins residing in the nerve terminal, the synaptic basal lamina, or in the postsynaptic region of the motor endplate. The disease proteins identified to date include the acetylcholine receptor, acetylcholinesterase, choline acetyltransferase, rapsyn, and Na(v)1.4, muscle-specific kinase, agrin, β2-laminin, downstream of tyrosine kinase 7, and glutamine-fructose-6-phosphate transaminase 1. Analysis of electrophysiologic and biochemical properties of mutant proteins expressed in heterologous systems have contributed crucially to defining the molecular consequences of the observed mutations and have resulted in improved therapy of most CMS.
先天性肌无力综合征 (CMS) 代表了一组异质性疾病，其中神经肌肉传递的安全裕度受到一种或多种特定机制的损害。临床、电生理和形态学研究为检测神经末梢、突触基底膜或运动终板突触后区域中存在的蛋白质中的 CMS 相关突变铺平了道路。迄今为止鉴定的疾病蛋白包括乙酰胆碱受体、乙酰胆碱酯酶、胆碱乙酰转移酶、rapsyn 和 Na(v)1.4、肌肉特异性激酶、神经节苷脂、β2-层粘连蛋白、酪氨酸激酶 7 的下游和谷氨酰胺-果糖-6-磷酸转氨基酶 1。在异源系统中表达的突变蛋白的电生理和生化特性分析对确定观察到的突变的分子后果至关重要，并导致大多数 CMS 的治疗得到改善。
