难治性癫痫患儿的基因变异特征分析  

Characterization of genetic variants in children with refractory epilepsy

作　　者：王凯旋 蔡丹丹 盛放 王大燕[1] 钱旭波 张静[1] 姜雪燕 徐丽丹 许焱婷 Wang Kaixuan;Cai Dandan;Sheng Fang;Wang Dayan;Qian Xubo;Zhang Jing;Jiang Xueyan;Xu Lidan;Xu Yanting(Department of Pediatrics,Affiliated Jinhua Hospital of Zhejiang University School of Medicine,Jinhua Municipal Central Hospital,Jinhua,Zhejiang 321099,China;Hangzhou Juno Genomics Inc.,Hangzhou,Zhejiang 310018,China)

机构地区：[1]浙江大学医学院附属金华医院(金华市中心医院)儿科,金华321099 [2]杭州金诺医学检验实验室有限公司,杭州310018

出　　处：《中华医学遗传学杂志》2023年第10期1204-1210,共7页Chinese Journal of Medical Genetics

基　　金：浙江省医药卫生科技计划(2018ZD053)。

摘　　要：目的分析不同年龄段难治性癫痫(RE)患儿的基因变异特征,为精准诊疗提供一定的数据支撑。方法选取2018年1月1日至2019年11月21日于浙江大学医学院附属金华医院就诊的117例RE患儿为研究对象,根据发病年龄分为<1岁、1~<3岁、3~<12岁和≥12岁4组。回顾性分析患儿的临床资料、全外显子组测序数据、携带基因变异患儿的父母测序结果等资料。结果本研究纳入RE患者共117例,其中男性67例,女性50例。发病年龄范围为4日龄~14岁。117例RE患儿中,33例携带致病性或可能致病性变异,检出率为28.21%(33/117)。<1岁组、1~<3岁组和≥3岁组的检出率分别为53.85%(21/39)、12.00%(3/25)和16.98%(9/53),差异有统计学意义(χ^(2)=19.202,P<0.001)。有、无共患病患儿的检出率分别为33.33%(12/36)和25.93%(21/81),差异无统计学意义(χ^(2)=0.359,P=0.549)。33例携带基因变异患儿中,27例为单核苷酸多态性变异(SNV)或插入缺失(InDel)变异,6例为拷贝数变异(CNV)。检出率最高的变异基因为PRRT2(15.15%,5/33),其次为SCN1A(12.12%,4/33)。携带基因变异的患儿中,72.73%(8/11)的患儿根据参考文献调整药物后获得临床缓解。结论28.21%的RE患儿可检出致病或可能致病CNV变异,发病年龄小的患儿检出率较高,PRRT2和SCN1A基因受累较多见。根据受累基因的类型调整药物将有助于提高缓解率。Objective To analyze the characteristics of genetic variants among children with refractory epilepsy(RE).Methods One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1,2018 to November 21,2019 were selected as the study subjects.The children were divided into four groups according to their ages of onset:<1 year old,1~<3 years old,3~<12 years old,and≥12 years old.Clinical data and results of trio-whole exome sequencing were retrospectively analyzed.Results In total 67 males and 50 females were included.The age of onset had ranged from 4 days to 14 years old.Among the 117 patients,33(28.21%)had carried pathogenic or likely pathogenic variants.The detection rates for the<1 year old,1~<3 years old and≥3 years old groups were 53.85%(21/39),12.00%(3/25)and 16.98%(9/53),respectively,with a significant difference among the groups(χ^(2)=19.202,P<0.001).The detection rates for patients with and without comorbidities were 33.33%(12/36)and 25.93%(21/81),respectively(χ^(2)=0.359,P=0.549).Among the 33 patients carrying genetic variants,27 were single nucleotide polymorphisms(SNPs)or insertion/deletion(InDel),and 6 were copy number variations(CNVs).The most common mutant genes were PRRT2(15.15%,5/33)and SCN1A(12.12%,4/33).Among children carrying genetic variants,72.73%(8/11)had attained clinical remission after adjusting the medication according to the references.Conclusion 28.21%of RE patients have harbored pathogenic or likely pathogenic variants or CNVs.The detection rates are higher in those with younger age of onset.PRRT2 and SCN1A genes are more commonly involved.Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.

关 键 词：难治性癫痫 儿童 全外显子组测序 单核苷酸多态性变异 插入缺失变异 拷贝数变异 

分 类 号：R742.1[医药卫生—神经病学与精神病学]