1例SCN8A突变所致患儿癫痫局灶性发作的遗传学分析  

Genetic analysis of case of focal seizures in a child with epilepsy due to SCN8A mutation

作　　者：成子安 段丽芬[2] 王晓辉[1] 边成 褚嘉佑[1] 杨昭庆[1] CHENG Zian;DUAN Lifen;WANG Xiaohui;BIAN Cheng;CHU Jiayou;YANG Zhaoqing(Laboratory of Medical Genetics,Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming,Yunnan 650118,China;Epilepsy Center,Kunming Children's Hospital,Kunming,Yunnan 650034,China)

机构地区：[1]中国医学科学院&北京协和医学院医学生物学研究所医学遗传学研究室,云南昆明650118 [2]昆明市儿童医院癫痫中心,云南昆明650034

出　　处：《中国优生与遗传杂志》2023年第12期2525-2529,共5页Chinese Journal of Birth Health & Heredity

基　　金：云南省高层次卫生健康技术人才项目(L-2018003);云南省科技厅重大科技专项计划(202102AA100021-5);云南省科技厅昆明医科大学应用基础研究联合专项资金面上项目(202001AY070001-273);中国抗癫痫协会癫痫科研基金(CQ-B-2021-04);昆明市卫生科技人才培养项目暨“十百千”工程培养计划项目[2021-SW(省)-23]。

摘　　要：目的探讨1个癫痫患儿的临床表现及遗传学病因。方法收集先证者的临床资料,采用全外显子组测序技术(WES)对先证者以及其双亲的外周血来源DNA进行基因变异检测,筛选患儿致病突变,并通过Sanger DNA测序法进行验证;利用蛋白功能预测软件(SIFT&PROVEAN、POLYPHEN2、MUTATIONTASTER)和DNAMAN软件分别对候选基因突变导致的蛋白功能改变以及蛋白位点保守性进行生物信息学分析,UCSF Chimera(Universityof California,San Francisco Chimera)对突变位置的蛋白结构进行了分析。结果先证者临床表现为癫痫局灶性发作,结构性左侧海马体发育异常。检测出先证者SCN8A基因(NM_014191)第10外显子存在c.1243G>A:pE415K的新生杂合突变,该突变位于电压门控通道Nav1.6的拓扑结构域1上,可能会影响神经元活性,钠离子通道失活等,此前未见报道。结论本研究确定了该癫痫局灶性发作患儿的病因为SCN8A基因突变,阐释了该患者出现的原因,进一步丰富了癫痫发作的基因突变谱。Objective To examine the clinical presentation and genetic cause of a child with epilepsy.Methods Clinical data for the subject were collected,and the proband's genetic variations,as well as those of the parents,were identified using whole exome sequencing(WES).Sanger DNA sequencing was used to confirm the presence of potentially pathogenic mutations.Protein function prediction tools(SIFT&PROVEAN,POLYPHEN2,MUTATION TASTER)and DNAMAN software were employed to analyze how these mutations may alter protein function and assess protein site conservativeness.UCSF Chimera was used to analyze the protein structure at the mutation site.Results The proband exhibited focal seizures and structural abnormalities in the left hippocampus.WES revealed a de novo heterozygous mutation of c.1243G>A:pE415K in exon 10 of the SCN8A gene(NM_014191)in the proband.This mutation is located on topology domain 1 of the Voltage-gated channel Nav1.6 and may impact neuronal activity and sodium channel inactivation,among other functions.To our knowledge,this mutation has not been previously reported.Conclusion This study identified a pathogenic mutation in the SCN8A gene responsible for focal seizures,expanding the spectrum of gene mutations associated with seizures.

关 键 词：癫痫 SCN8A基因 基因突变 全外显子组测序 

分 类 号：R742.1[医药卫生—神经病学与精神病学]