摘要
目的探讨KCNQ2基因突变相关癫痫临床表型与基因型的相关性。方法收集2015年10月至2018年9月经全外显子组测序技术筛选出的10例KCNQ2基因阳性突变患儿的临床资料,其中包括一对异卵双胞胎。被证实的突变均用Sanger测序验证,并明确突变的父母来源。结果发现5个新的KCNQ2突变,c.1720_1721delGG、c.185C>T、c.2180A>G、c.2245G>A、c.1164A>T,另外3个已报道突变c.917C>T、c.1687G>A、c.1741C>T。患儿表现为轻重不一的早发性癫痫脑病(EOEE)。在双胞胎患儿中均发现无义突变c.807G>A,但1例临床诊断为EOEE,另1例为良性家族性新生儿癫痫。家系调查发现家族中5人受累,受累者的临床表现轻重不一。10例患儿经单药或联合苯巴比妥、丙戊酸钠、托吡酯、奥卡西平、左乙拉西坦治疗后,大部分症状改善或消失。结论KCNQ2基因相关癫痫是一种谱系疾病,可从重型的EOEE到中间型的非典型早发癫痫脑病及良性家族性婴儿癫痫,再到轻型的良性家族性新生儿癫痫等。KCNQ2基因突变类型及位点分布可能与临床表型相关联,需要个体化治疗。
Objective To investigate the correlation between clinical phenotype and genotype in children with epilepsy associated with KCNQ2 gene mutation.Methods 10 EOEE(early-onset epileptic encephalopathy)patients including a pair of twins with KCNQ2 mutations were studied.Whole-exome sequencing(WES)was performed to identify genetic change and relevant clinical features were collected.Sanger sequencing was performed to confirm variants detected by WES.Clinical features were evaluated by neurological specialists.EEG,MRI and treatment information were collected accordingly.Results Ten(10)patients with KCNQ2 mutations were reported in our study.WES identified 5 novel KCNQ2 mutations(c.1720_1721delGG,c.185C>T,c.2180A>G,c.2245G>A,c.1164A>T),and three reported mutations(c.917C>T,c.1687G>A,c.1741C>T)in 10 patients with early-onset epilepsy encephalopathy.In twin patients with stop-gain mutation of c.807G>A,one presented with benign familial neonatal seizures,while the other with EOEE.Five of other six family members of the twins investigated were c.807G>A mutation carriers.Ten patients underwent single-agent or combination therapy with phenobarbital,sodium valproate,topiramate,oxcarbazepine,and levetiracetam.For most patients,the symptoms were improved with less frequent or no seizures.Conclusion KCNQ2 gene-associated epilepsy is a lineage disease,and KCNQ2 mutations can lead to a variety of clinical phenotypes ranging from the heaviest EOEE to the mildest familial neonatal epilepsy.The type and site distribution of KCNQ2 gene mutations may be associated with clinical phenotypes.Individualized treatment is extremely important for KCNQ2 mutation-related epilepsy.
作者
方红军
冯枚
胡文静
唐静文
杨赛
杨理明
FANG Hongjun;FEI Mei;HU Wenjing;TANG Jingwen;YANG Sai;YANG Liming(The Children’s Hospital of Hunan Province,Changsha 410007,Hunan,China)
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2019年第11期816-819,共4页
Journal of Clinical Pediatrics
基金
湖南省卫生健康委2019年度科研计划课题项目（No.C2019010）
关键词
早发性癫痫脑病
KCNQ2基因
突变
early onset epilepsy encephalopathy
KCNQ2 gene
gene mutations
