Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment.
Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment.
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先天性肌关系综合征：发病机理，诊断和治疗。
DOI：
10.1016/s1474-4422(14)70201-7
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Sine SM
中科院分区：
文献类型：
--
作者：
Engel AG;Shen XM;Selcen D;Sine SM
先天性肌无力综合征是由运动终板异常信号传递联系在一起的多种疾病，这些异常信号传递源于单个或多个蛋白质的缺陷。多个终板蛋白受蛋白糖基化所需的单个酶突变的影响，PREPL的缺失通过激活衔接蛋白1发挥其作用。最后，在某些先天性肌病中，神经肌肉传递也受损。某些综合征的特异性诊断是通过指向疾病基因的临床线索来促进的。在缺乏这些线索的情况下，外显子组测序是发现疾病基因的有用工具。对疾病机制的更深入理解来自于对患者终板的结构和体外电生理学研究，以及将突变体和野生型基因工程化到合适的表达系统中，所述表达系统可以通过适当的电生理学和生物化学研究来询问。大多数CMS是可以治疗的。然而，重要的是，一些对一种综合征有益的药物可能对另一种综合征有害。
The congenital myasthenic syndromes are diverse disorders linked by abnormal signal transmission at the motor endplate that stem from defects in single or multiple proteins. Multiple endplate proteins are affected by mutations of single enzymes required for protein glycosylation, and deletion of PREPL exerts its effect by activating adaptor protein 1. Finally, neuromuscular transmission is also impaired in some congenital myopathies. The specific diagnosis of some syndromes is facilitated by clinical clues pointing to a disease gene. In absence of such clues, exome sequencing is a useful tool for finding the disease gene. Deeper understanding of disease mechanisms come from structural and in vitro electrophysiologic studies of the patient endplate, and from engineering the mutant and wild-type gene into a suitable expression system that can be interrogated by appropriate electrophysiologic and biochemical studies. Most CMS are treatable. Importantly, however, some medication beneficial in one syndrome can be detrimental in another.