Ohno Kinji, Ito Mikako, Ohkawara Bisei
Graudate School of Nutritional Sciences, Nagoya University of Arts and Sciences, Nisshin, Japan.
Division of Neurogenetics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Hum Genet. 2025 Jun 18. doi: 10.1038/s10038-025-01355-9.
Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by compromised neuromuscular signal transmission due to pathogenic germline variants in genes expressed at the neuromuscular junction (NMJ). A total of 40 genes have been reported in CMS (AGRN, ALG14, ALG2, CHAT, CHD8, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, COL13A1, COLQ, DES, DOK7, DPAGT1, GFPT1, GMPPB, LAMA5, LAMB2, LRP4, MACF1, MUSK, MYO9A, PLEC, PREPL, PTPN11, PURA, RAPSN, RPH3A, SCN4A, SLC18A3, SLC25A1, SLC5A7, SNAP25, SYT2, TEFM, TOR1AIP1, UNC13A, UNC50 and VAMP1). The 40 genes are putatively classified into 13 subtypes by pathomechanical, clinical, and therapeutic features. A unique feature shared by recently identified genes is that CMS is concomitantly recognized in other mostly severer diseases. For example, four recently identified genes exhibit the following phenotypes: PURA-CMS, developmental delay; TEFM-CMS, mitochondrial disease; PTPN11-CMS, Noonan syndrome/Leopard syndrome; and DES-CMS, desmin myopathy. Conversely, these diseases are not always associated with CMS, although genetic and/or environmental factors that determine the involvement of the NMJ remain to be identified. In this review, particular emphasis will be placed on five recently identified genes (MACF1, TEFM, PTPN11, DES and UNC50).
先天性肌无力综合征（CMS）是一组异质性疾病，其特征是由于神经肌肉接头（NMJ）处表达的基因发生致病性种系变异，导致神经肌肉信号传递受损。CMS中已报道了40个基因（AGRN、ALG14、ALG2、CHAT、CHD8、CHRNA1、CHRNB1、CHRND、CHRNE、CHRNG、COL13A1、COLQ、DES、DOK7、DPAGT1、GFPT1、GMPPB、LAMA5、LAMB2、LRP4、MACF1、MUSK、MYO9A、PLEC、PREPL、PTPN11、PURA、RAPSN、RPH3A、SCN4A、SLC18A3、SLC25A1、SLC5A7、SNAP25、SYT2、TEFM、TOR1AIP1、UNC13A、UNC50和VAMP1）。根据病理力学、临床和治疗特征，这40个基因被初步分为13个亚型。最近发现的基因共有的一个独特特征是，CMS在其他大多更严重的疾病中也同时被识别出来。例如，最近发现的四个基因表现出以下表型：PURA - CMS，发育迟缓；TEFM - CMS，线粒体疾病；PTPN11 - CMS，努南综合征/豹皮综合征；以及DES - CMS，结蛋白肌病。相反，这些疾病并不总是与CMS相关，尽管决定NMJ受累的遗传和/或环境因素仍有待确定。在本综述中，将特别强调最近发现的五个基因（MACF1、TEFM、PTPN11、DES和UNC50）。
