GRIN2B基因错义变异致早发性癫痫性脑病27型1例报告  

Early-onset epileptic encephalopathy type 27 caused by missense variation of GRIN2B gene:a case report

作　　者：梅道启 梅世月 王潇娜 王媛[1] 陈国洪 杨志晓[1] 陈晓轶 张耀东 杨秀安 MEI Daoqi;MEI Shiyue;WANG Xiaona;WANG Yuan;CHEN Guohong;YANG Zhixiao;CHEN Xiaoyi;ZHANG Yaodong;YANG Xiuan(Department of Neurology,Children's Hospital Affiliated to Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou 450018,Henan,China;Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases,Henan Engineering Research Center of Childhood Neurodevelopment,Zhengzhou 450018,Henan,China;China Department of Biochemistry,School of Basic Medical Science,Chengde Medical University,Chengde 067000,Henan,China)

机构地区：[1]郑州大学附属儿童医院(河南省儿童医院,郑州儿童医院)东区神经内科,河南郑州450018 [2]河南省遗传代谢性疾病重点实验室,河南省儿童神经发育工程研究中心,河南郑州450018 [3]承德医学院基础医学院生物化学教研室,河南承德067000

出　　处：《临床儿科杂志》2022年第4期300-305,共6页Journal of Clinical Pediatrics

基　　金：国家自然科学基金项目(No.81701125,No.81901387);河南省医学科技攻关计划联合共建项目(No.LHGJ20200618,No.LHGJ20190914,No.2018020633,No.2018020603,No.2018020616);河南省科技攻关计划项目(No.202102310070);河南省高等学校重点科研项目计划(No.18A310029);河南省儿童神经发育工程研究中心开放课题(No.SG201907)。

摘　　要：早发性癫痫性脑病(EOEE)是新生儿期或婴儿早期出现的的一种癫痫综合征,具有遗传异质性,表现为早发性、难治性和多种发作类型及全面发育迟滞或倒退等特征。文章回顾分析1例确诊GRIN2B基因变异致EOEE 27型患儿的临床资料。患儿为12月龄女童,生后第2天起病,表现为难治性癫痫、精神运动发育迟缓、肌张力低下。头颅磁共振示双侧额部蛛网膜下腔增宽;长程视频脑电图示醒-睡各期均有多灶性尖波、棘波发放,有与临床发作同期的脑部异常放电,提示睡眠期右侧额叶、中央区尖波、棘慢波发放。全外显子基因测序发现患儿GRIN2B基因存在新生杂合错义变异c.2635G>A(p.Glu 879Lys)(NM_000834),父母及哥哥基因型为野生型,关联EOEE 27型,未见本位点变异相关文献报道。根据2015年美国医学遗传学与基因组学学会指南,判定为可能致病。患儿应用托吡酯、奥卡西平及康复功能训练治疗。随访患儿发育较正常同龄儿落后,无癫痫发作,脑电图未见异常放电。GRIN2B基因错义变异(NM_000834):c.2635G>A(p.Glu879Lys)是患儿的可能病因。Early-onset epileptic encephalopathy(EOEE)is a kind of epileptic syndrome that appears in neonatal period or early infancy.It has genetic heterogeneity and is characterized by early onset,refractory,multiple seizure types and overall developmental retardation or regression.The clinical data of a child with early-onset epileptic encephalopathy type 27 caused by GRIN2B gene variation were reviewed.The patient was a 12-month-old girl who developed the disease on the second day after birth,presenting with refractory epilepsy,psychomotor retardation,and hypotonia.Cranial magnetic resonance imaging showed bilateral frontal subarachnoid space widening.Long range video electroencephalogram showed multifocal sharp waves and spike waves in each waking and sleeping period,as well as abnormal brain discharges corresponding to the clinical onset,suggesting sharp waves and spike slow waves in the right frontal lobe and central region during sleeping period.Whole exon gene sequencing revealed a novel heterozygous missense variation of c.2635G>A(p.Glu879Lys)(NM_000834)in GRIN2B gene of the proband.The parental and elder brother genotypes were wild-type and the child was considered as early-onset epileptic encephalopathy type 27.No literature was reported on this locus variant.According to the 2015 guidelines of the American College of Medical Genetics and Genomics,it was considered likely pathogenic.Topiramate,ocasepine and rehabilitation function training were used for treatment.During the follow-up,the development of the patient was found to be behind that of normal children of the same age,and there was no epileptic seizure and no abnormal discharge in electroencephalogram.The GRIN2B gene missense variant of(NM_000834):c.2635G>A(p.Glu879Lys)is a possible cause of the proband.

关 键 词：GRIN2B基因 早发性癫痫性脑病 难治性癫痫 精神运动发育迟缓 儿童 

分 类 号：R742.1[医药卫生—神经病学与精神病学]