Ion Channel Genes and Epilepsy:Functional Alteration,Pathogenic Potential,and Mechanism of Epilepsy  

作　　者：Feng Wei Li-Min Yan Tao Su Na He Zhi-Jian Lin Jie Wang Yi-Wu Shi Yong-Hong Yi Wei-Ping Liao 

机构地区：[1]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 [2]Department of Neurology,Guangdong Second Provincial General Hospital

出　　处：《Neuroscience Bulletin》2017年第4期455-477,共23页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China (81571273,81571274,81501124,81271434,and 81301107);Omics-based precision medicine of epilepsy being entrusted by Key Research Project of the Ministry of Science and Technology of China (2016YFC0904400);the Natural Science Foundation of Guangdong Province,China (2014A030313489);Science and Technology Planning Projects of Guangdong Province,China (2012B031800404 and 2013B051000084);the Department of Education of Guangdong Province,China (2013CXZDA022,2013KJCX0156,and 2012KJCX009);the Foundation for High-level Talents in Higher Education of Guangdong Province,China (2013-167);Yangcheng Scholar Research Projects of Guangzhou Municipal College (12A016S and 12A017G);Science and Technology Projects of Guangzhou,Guangdong Province,China (2014J4100069,201508020011,201604020161,and 201607010002)

摘　　要：Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated 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-offunction 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.Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated 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-offunction 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.

关 键 词：EPILEPSY Ion channel gene Epilepsy gene GENETICS Gene function Pathogenic mechanism 

分 类 号：R742.1[医药卫生—神经病学与精神病学]