Molecular Genetic Laboratory, Wolfson Medical Center, Holon, Israel.
J Neurol Sci. 2012 May 15;316(1-2):112-5. doi: 10.1016/j.jns.2012.01.012. Epub 2012 Feb 10.
Congenital myasthenic syndromes (CMS) are rare genetic disorders characterized by impaired neuromuscular transmission. They are caused by mutations in synaptic, presynaptic and post synaptic proteins. Rapsyn is a postsynaptic peripheral membrane protein that anchors the nicotinic acetylcholine receptor to the motor endplate. CMS patients of Iraqi and Persian Jewish origin, carry a common founder mutation in the E box of the RAPSN promoter region (-38A-G) that causes impaired transcriptional activities of the promoter region. We describe a Persian Jewish family with two siblings affected with typical CMS, harboring the common heterozygous (-38A-G) E-box mutation associated with a previously unreported heterozygous p.224 insT causing an insertion of Threonine in the TPR6 domain. To the best of our knowledge, this is the first mutation in the TPR6 domain and might give supportive evidence to the role of this domain in rapsyn self association and consequently co-clustering with AchR in the post synaptic membrane.
先天性肌无力综合征（CMS）是一种罕见的遗传性疾病，其特征是神经肌肉传递受损。它们是由突触、突触前和突触后蛋白的突变引起的。Rapsyn 是一种突触后周围膜蛋白，将烟碱型乙酰胆碱受体锚定在运动终板上。伊拉克和波斯犹太人来源的 CMS 患者携带 RAPSN 启动子区域 E 盒中的常见创始突变（-38A-G），导致启动子区域的转录活性受损。我们描述了一个有两个受影响的兄弟姐妹的波斯犹太家族，他们携带有与先前未报道的杂合子 p.224 insT 相关的常见杂合子（-38A-G）E 盒突变，该突变导致 TPR6 结构域中的苏氨酸插入。据我们所知，这是 TPR6 结构域中的第一个突变，可能为该结构域在 rapsyn 自我关联中的作用提供支持证据，并因此与突触后膜中的 AchR 共同聚类。
