离子通道基因突变相关癫痫的临床特征及基因变异分析  

Analysis of clinical features and gene mutations in epilepsy caused by ion channel gene mutation

作　　者：孙莹[1] 段丽芬[1] 王惠萍[2] 王春霞[2] 叶磊[1] 余伟[1] 张艺 SUN Ying;DUAN Li-fen;WANG Hui-ping(Department of Epilepsy Center,Kunming Children’s Hospital(Yunnan Province Clinical Research Center for Children’s Health and Disease),Kunming 650000,China;不详)

机构地区：[1]昆明市儿童医院(云南省儿童健康与疾病临床医学研究中心)癫痫中心,650000 [2]昆明市儿童医院(云南省儿童健康与疾病临床医学研究中心)神经内科,650000

出　　处：《临床神经病学杂志》2023年第2期99-106,共8页Journal of Clinical Neurology

基　　金：云南省儿童健康与疾病临床医学研究中心对外开放研究基金(2022-ETYY-YJ-07);昆明市卫健委卫生科研课题(2022-06-01-011)。

摘　　要：目的分析离子通道基因变异相关癫痫的临床特征和基因变异特点,明确病因,精准选择抗癫痫药物。方法收集2019年9月至2021年5月昆明市儿童医院癫痫中心收治的病因不明的癫痫患者145例,采集患儿及其父母外周血样本,应用基因靶向二代测序技术进行癫痫基因测序分析,被证实的变异均用Sanger测序验证,并明确变异的来源,分析其中28例与致病性离子通道基因变异相关癫痫患者的基因型与临床特征。结果28例致病性离子通道基因相关癫痫患者中,钠离子通道相关基因变异者最多,共18例(64.3%),其中SCN1A基因变异14例,SCN8A基因变异2例,SCN2A基因变异2例;钾离子通道基因变异4例,其中KCNQ2变异3例,KCNH1变异1例;GABA受体门控通道基因变异4例,其中GABRG2基因变异3例,GABRB3基因变异1例;谷氨酸受体门控通道变异2例,均为GRIN2A基因变异。所有变异均为常染色体显性遗传,3例为遗传性变异,25例(89.3%)为新发杂合变异。所有变异中以错义变异最为常见(18/28,64.3%)。13例(46.4%)诊断为Dravet综合征,4例(14.2%)诊断为早发癫痫脑病,3例(10.7%)表现为良性新生儿癫痫,4例(14.3%)表现为全面性癫痫伴热性惊厥附加征,1例表现为Landau-Kleffner综合征,3例(10.7%)无法分类为特定癫痫综合征。大部分患者起病年龄早,71.4%(20/28)为1岁内起病,新生儿期起病者占1/4(7/28)。80%以上患者(23/28)病程中使用过2种或2种以上的抗癫痫药物治疗。随访4~72月,10例(35.7%)癫痫发作完全控制,1/2患者发作减少≥50%,3例(10%)发作减少<50%,1例死亡。结论离子通道基因变异是癫痫最常见的遗传性病因,可引起早发性癫痫性脑病,表现为起病年龄早、发作形式多样、药物难治、严重损害认知功能,也可表现为良性癫痫综合征,预后良好;以常染色体显性遗传、新发错义变异为主,临床上以钠离子通道基因变异最为多见,不同离子通道基因变异可有类似�Objective To analyze the clinical characteristics and gene mutations of epilepsy caused by ion channel gene mutation,identify the etiology and well guide the precise antiepileptic treatment.Methods The clinical data from 145 children with epilepsy with unknow etiology were collected and the peripheral blood of the patients and their parents were collected from September 2019 to May 2021 at the Department of Epilepsy center,Kunming Children’s Hospital.Epilepsy gene sequencing was performed by using disease gene targeting second generation sequencing technology.The mutation of pathogenic ion channel gene was found.The confirmed mutations were verified by Sanger sequencing and the source of the mutation was identified.Results Among the 28 patients with pathogenic ion channel gene-related epilepsy,18 patients(64.3%)had sodium ion channel gene mutation,which account for the majority of gene mutations,including 14 patients with SCN1A gene mutation,2 patients with SCN8A gene mutation and 2 patients with SCN2A gene mutation.There were 4 cases of potassium channel gene mutation,including 3 cases of KCNQ2 mutation and 1 case of KCNH1 mutation.GABA receptor gated channel gene mutation was found in 4 patients,including 3 with GABRG2 gene mutation and 1 with GABRB3 gene mutation.Two cases of glutamate receptor gated channel mutation were GRIN2A gene mutations.All the mutations were autosomal dominant,3 were inherited and 25(89.3%)were de nevo.Missense mutation was the most common(18/28,64.3%).Most cases were autosomal dominant inheritance and missense mutation.Dravet syndrome diagnosed in 13 cases(46.4%),4 cases(14.2%)diagnosed with early onset epileptic encephalopathy,3 cases(10.7%)of benign neonatal epilepsy,4 cases(14.3%)diagnosed as genetic epilepsy with febrile seizures plus,1 case presents as Landau-Kleffner syndrome,3 cases(10.7%)cannot be classified as specific epilepsy syndromes.The onset age of most patients were early,71.4%(20/28)onset at the first year of life,1/4(7/28)were in the neonatal period.More than 80%of

关 键 词：癫痫 离子通道 基因变异 

分 类 号：R742.1[医药卫生—神经病学与精神病学]