Inherited disorders of the neuromuscular junction: an update
Inherited disorders of the neuromuscular junction: an update
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DOI：
10.1007/s00415-014-7520-7
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发表时间：
2014-11-01
影响因子：
6
通讯作者：
Beeson, David
中科院分区：
文献类型：
--
作者：
Cruz, Pedro M. Rodriguez;Palace, Jacqueline;Beeson, David
先天性肌无力综合征（CMSs）是一组异质性遗传性疾病，由影响神经肌肉接头功能和结构的基因突变引起。这篇综述更新了读者对建立和新的亚型先天性肌无力，和治疗策略，这些日益异质性疾病。与N-糖基化途径和丝氨酸肽酶家族相关的突变的发现表明，编码普遍表达分子的致病基因可在人类神经肌肉接头处产生缺陷。相比之下，脂蛋白样受体4（LRP 4）的突变，先天性肌无力的长期候选基因，和一种新的表型的肌无力与远端无力和萎缩，由于AGRN的突变，现在已经被描述。此外，一个致病性剪接突变的CHRNA 1的非功能性外显子已被报道，强调在遗传分析中分析非功能性外显子的重要性。沙丁胺醇和麻黄碱单独使用或与吡啶斯的明或3，4-DAP联合使用对特定CMS亚型的获益越来越多。
Congenital myasthenic syndromes (CMSs) are a group of heterogeneous inherited disorders caused by mutations in genes affecting the function and structure of the neuromuscular junction. This review updates the reader on established and novel subtypes of congenital myasthenia, and the treatment strategies for these increasingly heterogeneous disorders. The discovery of mutations associated with the N-glycosylation pathway and in the family of serine peptidases has shown that causative genes encoding ubiquitously expressed molecules can produce defects at the human neuromuscular junction. By contrast, mutations in lipoprotein-like receptor 4 (LRP4), a long-time candidate gene for congenital myasthenia, and a novel phenotype of myasthenia with distal weakness and atrophy due to mutations in AGRN have now been described. In addition, a pathogenic splicing mutation in a nonfunctional exon of CHRNA1 has been reported emphasizing the importance of analysing nonfunctional exons in genetic analysis. The benefit of salbutamol and ephedrine alone or combined with pyridostigmine or 3,4-DAP is increasingly being reported for particular subtypes of CMS.