不明原因早发性癫痫脑病62例临床特点及相关基因突变分析  

Clinical features and gene mutations analysis in 62 children with early -onset epileptic encephalopathy of un- known causes

作　　者：胡春辉[1] 王龙飞[1] 王华[1] 

机构地区：[1]中国医科大学附属盛京医院小儿神经内科,沈阳110004

出　　处：《中华实用儿科临床杂志》2016年第5期371-375,共5页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的探讨不明原因早发性癫痫脑病（EOEE）患儿的临床表型特点，进行癫痫基因二代测序，寻找致病性突变。方法收集2013年6月至2015年6月62例不明原因EOEE患儿详细的临床资料，采集患儿及其父母外周血，应用疾病基因靶向二代测序技术进行癫痫基因测序分析，寻找可疑致病性突变，被证实的突变均用Sanger测序验证并明确突变的父母来源。结果62例不明原因EOEE患儿包括非特异性癫痫脑病37例（61％），婴儿痉挛症17例（27％），Dravet综合征6例（10％），大田原综合征1例（1％），早期肌阵挛脑病1例（1％）。17例婴儿痉挛症患儿未发现可疑致病突变。37例非特异性癫痫脑病患儿中，7例发现可疑致病突变，其中3例为PCDHl9基因错义突变，2例为CDKL5基因插入移码和剪切位点突变，1例为KCNQ2基因无义突变，1例为GRIN2A基因错义突变。1例KCNQ2基因无义突变患儿死亡。6例Dravet综合征患儿中，2例发现SCNIA基因插入移码突变（其中1例为新发突变），1例SCNlA基因错义突变，1例SCN9A基因错义突变，1例SCNlA基因合并SCN9A基因错义突变，突变位点在国际上均有相关报道。1例大田原综合征患儿发现STXBPl基因无义突变，为新发突变。1例早期肌阵挛脑病患儿未发现可疑致病突变。经治疗22例患儿癫痫控制，40例患儿癫痫未控制。结论不明原因EOEE患儿临床表型多样，国内发现致病基因SCNlA、SCN9A、STXBPl、PCDHl9、CDKL5、KCNQ2、GRIN2A基因与国际上已报道致病基因一致，部分基因突变为新发突变，SCN9A基因可能为Dravet综合征致病基因，KCNQ2基因无义突变可为致死性突变。Objective To study the clinical features and gene mutations of early - onset epileptic encephalo- pathy （EOEE） of unknown causes and to identify pathogenic mutations of EOEE by next generation sequencing. Methods The clinical data of 62 cases diagnosed with unexplained EOEE between June 2013 and June 2015 were ob- tained and analyzed. Specimens were collected from the selected children and their parents. Next generation sequencing was used to detect epilepsy- related genes, and Sangcr sequencing was performed to verify the results and confirm the source of the parents, further to identify suspected pathogenic mutations of EOEE. Results Among 62 cases with unex- plained EOEE,37 cases （61%） were diagnosed as non -specific EOEE,17 cases （27%） with West syndrome,6 ca- ses （ 10% ） with Dravet syndrome, 1 case（ 1% ） with Ohtahara syndrome, 1 case（ 1% ） with early myoclonic epileptic encephalopathy. The pathogenic mutations were not detected among 17 cases with West syndrome and the early myoclonic epileptic encephalopathy. Among 37 cases with non - specific EOEE, suspected pathogenic mutations were detected in 7 cases. Three cases of missense mutations for PCDH19 gene, 1 case of frame - shift mutation and 1 case of splice site mutation for CDKL5 gene, 1 case of denovo nonsense mutation for KCNQ2 gene, and 1 case of missense muta- tion for GRIN2A gene were detected. Among 6 children with Dravet syndrome, 2 cases of frame - shift mutations and 1 case of missense mutation for SCN1A gene were detected, of which 2 cases were of frame - shift mutations, 1 case was denovo mutation, 1 case of missense mutation for SCN1A gene and 1 case of missense mutation for SCNIA combined with SCN9A gene were detected. One case of denovo nonsense mutation for STXBP1 gene was detected. After treatment, 22 cases with clinical seizures were under control, and 40 cases were out of control. Conclusions The clinical pheno- types for children with unexplained EOEE were varied. SCN1A, SCN9A, STXBP1, PCDH19, CDKLS, KCNQ2 and

关 键 词：早发性癫痫脑病 DRAVET综合征 婴儿痉挛症 大田原综合征 基因 突变 

分 类 号：R742.1[医药卫生—神经病学与精神病学]