论文部分内容阅读
目的:探讨KCNQ2基因致病突变相关的癫痫临床特征，报道新的KCNQ2基因突变和临床表型，认识该基因导致的癫痫表型谱，为治疗选择及预后评估提供帮助。方法:于2015年7月至2019年10月就诊于首都儿科研究所附属儿童医院神经内科病房和门诊的979例癫痫和发育迟缓患者中，经全外显子组测序技术筛选出12个携带KCNQ2基因突变的家系，共13例患者。被证实的突变均用Sanger测序验证，并明确突变的父母来源。结合患者的测序结果分析其临床表型及基因型。结果:13例患者临床表型均为癫痫，>6月龄起病者4例，其中婴儿期2例（分类为癫痫性脑病），幼儿期1例（分类为癫痫性脑病），青少年期1例（良性癫痫）；8例应用奥卡西平治疗，5例无发作，2例发作次数减少>50%；2例单用托吡酯治疗无发作。基因型分析共发现5个新的KCNQ2基因突变，分别为c.379T>G（p.Y127D）、c.1A>C（起始密码子变异）、c.708G>C（p.W236C）、c.1027G>T（p.A343S）及c.1649T>G（p.V550G）。结论:虽然临床较为罕见，但KCNQ2基因变异在幼儿期起病和青少年期起病的癫痫患者中也存在。文中同时报道了KCNQ2基因的5个新突变，进一步扩大了其基因表型谱和基因谱。奥卡西平在KCNQ2基因突变相关癫痫的治疗中有效率较高，早期进行遗传学检测对癫痫治疗有显著帮助。“,”Objective:To report the clinical features of KCNQ2-associated epilepsy and the novel mutations and unreported clinical phenotype of KCNQ2 gene, so as to provide help for treatment selection and prognosis evaluation.Methods:Among 979 patients with epilepsy and developmental delay who were admitted to the Department of Neurology,Children′s Hospital Affiliated to Capital Institute of Pediatrics from July 2015 to October 2019, a total of 13 patients were selected from 12 families with KCNQ2 gene mutation by whole exome sequencing technology. Suspected mutations were verified by Sanger sequencing on the probands and their parents to identify the source. The clinical phenotype and genotype were analyzed according to these results.Results:Among the 13 patients with epilepsy, the onset age of four cases were older than six months [two cases in infancy (epilepsy encephalopathy), one case in early childhood (epilepsy encephalopathy) and one case in adolescence (benign epilepsy)]. Eight cases were treated with oxcarbazepine, of whom five cases were seizure free, and two cases showed partial response (>50%). Two cases treated with topiramate were seizure free. Five novel mutations were found in this research, including c.379T>G(p.Y127D), c.1A>C(initial codon mutation), c.708G>C(p.W236C), c.1027G>T(p.A343S) and c.1649T>G(p.V550G).Conclusions:Although it was rare in clinical work, the variation of KCNQ2 gene existed in patients with childhood-onset epilepsy and adolescent-onset epilepsy. Meanwhile, five novel mutations of KCNQ2 gene were reported, which further expanded its gene spectrum. This research supported that oxcarbazepine was the efficient medicine for the KCNQ2-associated epilepsy. Genetic testing showed great help to the treatment of epilepsy.