摘要
目的探讨经二代测序确诊的GRIN2A基因变异所致癫痫失语疾病谱患儿的临床表型特征及基因变异特点。方法回顾性分析2019年2月至2022年11月郑州大学附属儿童医院神经内科确诊的5例以癫痫起病的癫痫失语疾病谱患儿的临床资料,采用二代测序方法对先证者进行全外显子基因组测序,证实5例均为GRIN2A基因变异患儿,并通过一代Sanger测序对家系成员进行验证以确认变异来源,对GRIN2A基因变异特点进行分析。结果5例确诊为GRIN2A基因变异所致癫痫失语疾病谱的患儿中,男女比例为4∶1,起病年龄范围为1.5~4.4岁。临床表型均有癫痫发作,4例有语言及智能发育落后;3例共患有注意力缺陷多动障碍;癫痫发作表现为局灶性发作或继发全面性发作;应用抗癫痫药物均得到有效控制。5例患儿中例1的基因变异源于父亲杂合变异,例2~5均为新发变异,分别为c.2107C>T(p.Gln703*)无义变异、c.2284G>A(p.Gly762Arg)错义变异、c.2197del(p.Ala733Glnfs*3)移码变异、c.2511G>A(p.Trp837*)无义变异、c.1651+1G>C剪切位点变异。经查阅文献,5例的基因变异位点均未见相关报道。结论癫痫失语疾病谱是一种起病复杂的癫痫综合征,不同基因变异位点可能有不同表型,发作形式以局灶性发作为主,部分可继发全面性发作,应用抗癫痫药物能够有效控制发作。GRIN2A基因变异为癫痫失语疾病谱的遗传学病因。
Objective To explore the clinical phenotypic features and genetic variation characteristics of children with epilepsy-aphasia spectrum due to GRIN2A gene variants confirmed by second-generation sequencing.Methods The clinical data of 5 children with epilepsy-aphasia spectrum with epileptic onset diagnosed in the Department of Neurology,Children's Hospital Affiliated to Zhengzhou University,from February 2019 to November 2022 were retrospectively analyzed.Whole-exome genome sequencing of the probands using a second-generation sequencing method confirmed that all 5 cases were children with the GRIN2A gene variant.The characteristics of the GRIN2A gene variants were analyzed.Results Among the 5 children diagnosed with epileptic aphasia spectrum due to GRIN2A gene variants,the male-to-female ratio was 4∶1,and the age range of onset was 1.5-4.4 years.The clinical phenotype included seizures in all cases,language and intellectual developmental deficits in 4 cases,and attention deficit hyperactivity disorder in 3 cases.The seizures were manifested as focal seizures or secondary generalized seizures,and were effectively controlled with antiepileptic drugs.Among the 5 children,gene variant of case 1 was originated from a paternal heterozygous variant,and cases 2-5 had de novo variants,which were c.2107C>T(p.Gln703*)nonsense variant,c.2284G>A(p.Gly762Arg)missense variant,c.2197del(p.Ala733Glnfs*3)shifted coding variant,c.2511G>A(p.Trp837*)nonsense variant,and c.1651+1G>C shear site variant,respectively.None of the 5 loci were reported in the literature.Conclusions Epilepsy-aphasia spectrum is an epilepsy syndrome with a complex onset,and may have different phenotypes at different genetic variant loci,with focal seizures or secondary generalized seizures,which can be effectively controlled with anti-seizure medication.The GRIN2A gene variant is the genetic etiology of the epileptic aphasia spectrum.
作者
马昂
梅道启
张耀东
梅世月
王媛
马远宁
郭建梅
张文乾
段勇涛
Ma Ang;Mei Daoqi;Zhang Yaodong;Mei Shiyue;Wang Yuan;Ma Yuanning;Guo Jianmei;Zhang Wenqian;Duan Yongtao(Department of Pediatrics,Children's Hospital Affiliated to Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou 450018,China;Department of Neurology,Children's Hospital Affiliated to Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou 450018,China;Affiliated Children's Hospital of Zhengzhou University,Key Laboratory of Pediatric Inherited Metabolic Diseases in Henan Province,Engineering Research Center of Pediatric Neurodevelopment in Henan Province,Zhengzhou Engineering Research Center for Zebrafish Model Construction of Pediatric Diseases and Drug Screening,Zhengzhou 450018,China)
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2024年第2期123-132,共10页
Chinese Journal of Neurology
基金
河南省科技厅科技攻关计划项目(232102310077)
河南省医学科技攻关计划(联合共建项目)(LHGJ20200618,2018020633)
河南省医学教育项目(Wjlx2022144)。