Engel Andrew G, Ohno Kinji, Sine Steven M
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA.
Muscle Nerve. 2003 Jan;27(1):4-25. doi: 10.1002/mus.10269.
Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic basal lamina, and postsynaptic proteins. The presynaptic CMS are associated with defects that curtail the evoked release of acetylcholine (ACh) quanta or ACh resynthesis. Defects in ACh resynthesis have now been traced to mutations in choline acetyltransferase. A basal lamina CMS is caused by mutations in the collagenic tail subunit (ColQ) of the endplate species of acetylcholinesterase that prevent the tail subunit from associating with catalytic subunits or from becoming inserted into the synaptic basal lamina. Most postsynaptic CMS are caused by mutations in subunits of the acetylcholine receptor (AChR) that alter the kinetic properties or decrease the expression of AChR. The kinetic mutations increase or decrease the synaptic response to ACh and result in slow- and fast-channel syndromes, respectively. Most low-expressor mutations reside in the AChR epsilon subunit and are partially compensated by residual expression of the fetal type gamma subunit. In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane.
先天性肌无力综合征（CMS）源于突触前、突触基底膜和突触后蛋白的缺陷。突触前CMS与减少乙酰胆碱（ACh）量子诱发释放或ACh再合成的缺陷有关。现在已将ACh再合成缺陷追溯到胆碱乙酰转移酶的突变。基底膜CMS是由乙酰胆碱酯酶终板型的胶原尾亚基（ColQ）突变引起的，这些突变阻止尾亚基与催化亚基结合或插入突触基底膜。大多数突触后CMS是由乙酰胆碱受体（AChR）亚基的突变引起的，这些突变改变了动力学特性或降低了AChR的表达。动力学突变分别增加或减少对ACh的突触反应，导致慢通道和快通道综合征。大多数低表达突变存在于AChRε亚基中，并由胎儿型γ亚基的残余表达部分补偿。在一部分CMS患者中，终板AChR缺乏是由rapsyn突变引起的，rapsyn是一种在将AChR集中于突触后膜中起关键作用的分子。
