Neuromotor synapses in Escobar syndrome.
Neuromotor synapses in Escobar syndrome.
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埃斯科瓦尔综合征的神经运动突触。
DOI：
10.1002/ajmg.a.36154
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Akins,RobertE
中科院分区：
文献类型：
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作者：
Robinson,KarynG;Viereck,MatthewJ;Margiotta,MeganV;Gripp,KarenW;Abdul-Rahman,OmarA;Akins,RobertE
多发性翼状胬肉综合征的 Escobar 变体 (OMIM #265000) 是一种罕见的常染色体隐性遗传疾病，与烟碱乙酰胆碱受体 (CHRNG) 的 γ 亚基突变相关。CHRNG 在运动发育过程中在胎儿肌肉中表达，有助于神经肌肉接头 (NMJ) 的形成。尚未对 Escobar 综合征患者的 NMJ 结构和功能异常进行研究。我们报告了来自四个家庭的五名被确定患有埃斯科瓦尔综合征的患者。在三个家族中，CHRNG 中发现了相同的突变 (c.459dupA)。从这些家庭之一的患者身上采集了肱桡肌活检样本，并使用荧光显微镜分析了 NMJ 组织。与特发性脊柱侧凸或脑瘫 (CP) 对照患者的脊柱肌肉相比，埃斯科巴综合征患者的乙酰胆碱酯酶外部乙酰胆碱受体的程度显着较高，而乙酰胆碱酯酶外部的乙酰胆碱酯酶的水平显着较低。鉴于乙酰胆碱受体γ亚基在胎儿神经肌肉信号转导以及建立肌肉和运动神经末梢的主要接触中的作用，Escobar综合征中描述的CHRNG突变可能会导致突触后蛋白更广泛的破坏，并由于产前神经肌肉传递受损和/或神经肌肉突触发生异常而导致NMJ异常发育。 © 2013 Wiley 期刊公司。
The Escobar variant of multiple pterygium syndrome (OMIM #265000) is a rare, autosomal recessive disorder associated with mutations in the γ‐subunit of the nicotinic acetylcholine receptor (CHRNG).CHRNGis expressed in fetal muscle during motor development and contributes to the formation of neuromuscular junctions (NMJs). Anomalies in NMJ structure and function have not been investigated in patients with Escobar syndrome. We report five patients identified as having Escobar syndrome, from four families. In three families, the same mutation (c.459dupA) was identified inCHRNG. A biopsy from brachioradialis muscle was collected from a patient from one of these families and analyzed for NMJ organization using fluorescence microscopy. Compared to spinalis muscle from control patients with idiopathic scoliosis or cerebral palsy (CP), the patient with Escobar syndrome had a significantly higher degree of acetylcholine receptor present outside acetylcholinesterase and significantly less acetylcholinesterase outside acetylcholine receptors. Given the role of the acetylcholine receptor γ‐subunit in fetal neuromuscular signal transduction and in establishing the primary encounter of muscle and motor nerve terminal, theCHRNGmutations described in Escobar syndrome may cause a broader disruption of postsynaptic proteins and result in aberrant development of the NMJ due to impaired prenatal neuromuscular transmission and/or abnormal neuromuscular synaptogenesis. © 2013 Wiley Periodicals, Inc.