Wei Feng, Yan Li-Min, Su Tao, He Na, Lin Zhi-Jian, Wang Jie, Shi Yi-Wu, Yi Yong-Hong, Liao Wei-Ping
Institute of Neuroscience, Department of Neurology of The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and Ministry of Education of China, Guangzhou Medical University, Guangzhou, 510260, China.
Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China.
Neurosci Bull. 2017 Aug;33(4):455-477. doi: 10.1007/s12264-017-0134-1. Epub 2017 May 9.
Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsy-associated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations (funotypes), and phenotypes of these mutations. Eleven genes featured loss-of-function mutations and six had gain-of-function mutations. Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.
离子通道在神经系统兴奋性的产生和调节中起着关键作用，并且与人类癫痫有关。本文系统综述了41个与癫痫相关的离子通道基因及其突变。我们分析了这些突变的基因型、功能改变（功能型）和表型。11个基因具有功能丧失突变，6个具有功能获得突变。9个基因表现出多样化的功能型，其中在SCN1A中发现了独特的功能型-表型相关性。这些数据表明，功能型是评估突变致病性时的一个重要考虑因素，独特的功能型或功能型-表型相关性有助于确定一个基因的致病潜力。
