No. 9

Title: Diverse pathophysiologic mechanisms of congenital defects of neuromuscular signal transmission

先天性神经肌肉信号传递缺陷的多种病理生理机制

Speaker: Xin-Ming Shen （沈新明）

Associate Professor of Neurology, Mayo Clinic Alix School of Medicine

Host：Lin Mei

           Chinese Institutes for Medical Research, Beijing

Time：10:00-11:30 a.m., Nov. 15, 2023 (Wednesday)

Location: Room 1322, North Tower, Basic Research Building, Capital Medical University (首都医科大学基础科研楼北楼1322会议室)

Abstract：

Congenital myasthenic syndromes (CMS) are a diverse array of disorders characterized by fatigable muscle weakness due to abnormal neuromuscular transmission caused by variants of more than 30 genes, which encode proteins in presynaptic, synaptic, and/or postsynaptic regions. The treatment of CMS solely depends on the distinct functional characterization of disease-causing variants as some drugs that are beneficial in one syndrome can be detrimental in another despite similar clinical symptoms. The lecture will discuss how to characterize the pathophysiologic mechanisms of CMS by employing multiple tools. These characterizations guide diagnosis and appropriate treatment for individual patients. Given half of CMS arise from mutations of acetylcholine receptor (AChR) subunits, the speaker will use AChR mutations as an example to discuss how the investigation of pathogenic variants of AChR subunits provides opportunities to explore new attributes in normal physiologic mechanisms of the mutant proteins.

先天性肌无力综合征 (CMS) 是一系列以疲劳性肌无力为特征的疾病，其病因是位于突触前、突触间隙、和/或突触后区域蛋白质的编码基因变异导致神经肌肉传递异常。CMS的治疗取决于对致病变异的病理机制的鉴定, 因为某些对一种综合征有益的药物可能对另一种综合征有害。本讲座将讨论如何通过使用多种方法来鉴定CMS的病理生理机制，从而指导个体患者的诊断和提供适当的治疗方案。鉴于一半的CMS病人源于乙酰胆碱受体（AChR)亚基的突变，讲者还将以AChR突变为例，讨论对AChR亚基致病性变异的机制研究如何为探索突变蛋白正常生理机制提供机会。

Representative publications:

Shen et al, Ann Clin Transl Neurol. 2023, 10: 732-743

Di et al, Neurology. 2020, 95: e2781

Shen et al, Exp Neurol. 2020, 331:113375

Shen et al, JCI Insight. 2018, 3: e97826

Engel et al, Lancet Neurol. 2015, 14: 420