Müller Juliane S, Mihaylova Violeta, Abicht Angela, Lochmüller Hanns
Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.
Expert Rev Mol Med. 2007 Aug 9;9(22):1-20. doi: 10.1017/S1462399407000427.
The neuromuscular junction (NMJ) is a complex structure that efficiently communicates the electrical impulse from the motor neuron to the skeletal muscle to induce muscle contraction. Genetic and autoimmune disorders known to compromise neuromuscular transmission are providing further insights into the complexities of NMJ function. Congenital myasthenic syndromes (CMSs) are a genetically and phenotypically heterogeneous group of rare hereditary disorders affecting neuromuscular transmission. The understanding of the molecular basis of the different types of CMSs has evolved rapidly in recent years. Mutations were first identified in the subunits of the nicotinic acetylcholine receptor (AChR), but now mutations in ten different genes - encoding post-, pre- or synaptic proteins - are known to cause CMSs. Pathogenic mechanisms leading to an impaired neuromuscular transmission modify AChRs or endplate structure or lead to decreased acetylcholine synthesis and release. However, the genetic background of many CMS forms is still unresolved. A precise molecular classification of CMS type is of paramount importance for the diagnosis, counselling and therapy of a patient, as different drugs may be beneficial or deleterious depending on the molecular background of the particular CMS.
神经肌肉接头（NMJ）是一种复杂的结构，它能有效地将电冲动从运动神经元传递到骨骼肌，从而诱发肌肉收缩。已知会损害神经肌肉传递的遗传和自身免疫性疾病，正为深入了解神经肌肉接头功能的复杂性提供更多线索。先天性肌无力综合征（CMSs）是一组在遗传和表型上具有异质性的罕见遗传性疾病，会影响神经肌肉传递。近年来，对不同类型先天性肌无力综合征分子基础的认识发展迅速。突变最初是在烟碱型乙酰胆碱受体（AChR）的亚基中发现的，但现在已知十个不同基因（编码突触后、突触前或突触蛋白）中的突变会导致先天性肌无力综合征。导致神经肌肉传递受损的致病机制会改变乙酰胆碱受体或终板结构，或导致乙酰胆碱合成和释放减少。然而，许多先天性肌无力综合征类型的遗传背景仍未明确。准确的先天性肌无力综合征分子分类对于患者的诊断、咨询和治疗至关重要，因为根据特定先天性肌无力综合征的分子背景，不同的药物可能有益或有害。
