Ohno K, Anlar B, Ozdirim E, Brengman J M, DeBleecker J L, Engel A G
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Ann Neurol. 1998 Aug;44(2):234-41. doi: 10.1002/ana.410440214.
We report and functionally characterize five new mutations of the acetylcholine receptor (AChR) in 11 Turkish patients with recessive congenital myasthenic syndromes (CMS) belonging to six families. All mutations are in the epsilon-subunit gene. Parental consanguinity is present in three families. The disease cosegregates with homozygous mutations in five families and with two different heteroallelic mutations in one family. Four mutations are frameshifting, predicting truncation of the epsilon subunit, and one occurs at a splice donor site. Expression of each frameshifting mutation and the likely transcripts of the splice-site mutation in human embryonic kidney 293 cells shows that each mutation is a null mutation. The findings support the notion that loss-of-function mutations of the acetylcholine receptor causing CMS are concentrated in the epsilon subunit, and that such mutations are a frequent cause of CMS.
我们报告并从功能上描述了11名来自6个家族的患有隐性先天性肌无力综合征（CMS）的土耳其患者中乙酰胆碱受体（AChR）的5种新突变。所有突变均位于ε亚基基因中。3个家族存在父母近亲结婚情况。该疾病在5个家族中与纯合突变共分离，在1个家族中与两种不同的杂合等位基因突变共分离。4种突变是移码突变，预测ε亚基会被截断，1种突变发生在剪接供体位点。在人胚肾293细胞中对每种移码突变以及剪接位点突变的可能转录本进行表达，结果表明每种突变都是无效突变。这些发现支持了这样一种观点，即导致CMS的乙酰胆碱受体功能丧失突变集中在ε亚基中，并且此类突变是CMS的常见病因。
