Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by ε-AChR subunit truncating mutations
Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by ε-AChR subunit truncating mutations
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DOI：
10.1007/s004390000359
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发表时间：
2000-08-01
期刊：
影响因子：
5.3
通讯作者：
Steinlein, OK
中科院分区：
文献类型：
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作者：
Sieb, JP;Kraner, S;Steinlein, OK
先天性肌无力综合征(CMS)是由突触前、突触或突触后神经肌肉传递缺陷引起的先天性疾病。一些先前描述的具有CMS典型体征的亲缘关系显示，神经肌肉接头处的乙酰胆碱受体(AChR)和促性腺激素明显缺乏。此外，终板超微结构不成熟，突触后膜包裹减少。在两个这样的家族中，我们发现了epsilon-AChR亚单位的截断突变。在家族1中，两个受影响的兄弟姐妹都是AChR epsilon亚单位基因(CHRNE)内的epsilon 911delT和epsilon IVS4+1G->；A突变的异等位基因。在家族2的受累成员中，发现了epsilon 1030delC突变和先前描述的epsilon R64X突变。这些有害的epsilon AChR突变不仅导致AChR缺乏。但也影响终板成熟，包括个体发育过程中次级突触裂隙的形成。
Congenital myasthenic syndromes (CMS) are inborn disorders due to presynaptic, synaptic, or postsynaptic defects of neuromuscular transmission. Some previously described kinships with typical signs of CMS showed a marked deficiency of acetylcholine receptors (AChR) and utrophin at the neuromuscular junctions. Additionally, the end-plate ultrastructure was immature, with reduced enfolding of the postsynaptic membrane. In two such families, we found truncating mutations of the epsilon-AChR subunit. In family 1, both affected siblings were heteroallelic for a epsilon 911delT and a epsilon IVS4+1G-->A mutation within the AChR epsilon-subunit gene (CHRNE). In the affected member of family 2, a epsilon 1030delC mutation and a previously described epsilon R64X mutation were found. These deleterious epsilon AChR mutations not only result in AChR deficiency. but also affect end-plate maturation, including the formation of secondary synaptic clefts during ontogenesis.