The impact of human hyperekplexia mutations on glycine receptor structure and function.
The impact of human hyperekplexia mutations on glycine receptor structure and function.
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DOI：
10.1186/1756-6606-7-2
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发表时间：
2014-01-09
期刊：
影响因子：
3.6
通讯作者：
Lynch JW
中科院分区：
文献类型：
--
作者：
Bode A;Lynch JW
过度兴奋是一种罕见的神经系统疾病，其特征是新生儿张力过高，对意外刺激的过度惊吓反应，以及呼吸暂停、智力残疾和语言获得延迟的可变发生率。大多数运动缺陷都可以通过氯硝西泮成功治疗。过度兴奋是由遗传性突变引起的，这种突变破坏了脊髓和脑干神经运动通路中抑制性甘氨酸能突触的功能。人类甘氨酸受体α1和β亚基在这些突触中占主导地位，是突变的主要靶点。国际遗传筛查计划，一起分析了几百个先证者，最近产生了一个清晰的图片基因型-表型相关性和不同类别的hyperekplexia突变的患病率。主要集中在这个新的信息，这篇综述旨在总结突变对甘氨酸受体结构和功能的影响，以及这些功能的改变如何导致hyperekplexia。
Hyperekplexia is a rare neurological disorder characterized by neonatal hypertonia, exaggerated startle responses to unexpected stimuli and a variable incidence of apnoea, intellectual disability and delays in speech acquisition. The majority of motor defects are successfully treated by clonazepam. Hyperekplexia is caused by hereditary mutations that disrupt the functioning of inhibitory glycinergic synapses in neuromotor pathways of the spinal cord and brainstem. The human glycine receptor α1 and β subunits, which predominate at these synapses, are the major targets of mutations. International genetic screening programs, that together have analysed several hundred probands, have recently generated a clear picture of genotype-phenotype correlations and the prevalence of different categories of hyperekplexia mutations. Focusing largely on this new information, this review seeks to summarise the effects of mutations on glycine receptor structure and function and how these functional alterations lead to hyperekplexia.