SCN1A基因新生无义突变导致Dravet综合征1例  

Dravet syndrome caused by a novel nonsense mutation of SCN1A gene locus:A case report

作　　者：赵柯 张耀东 王潇娜 马燕丽 耿伟光 缑灵山 ZHAO Ke;ZHANG Yaodong;WANG Xiaona;MA Yanli;GENG Weiguang;GOU Lingshan(Children's Hospital Affiliated to Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Henan Key Laboratory of Children's Genetics and Metabolic Diseases,Henan Children's Neurodevelopment Engineering Research Center,Zhengzhou,Henan 450018,China;Department of Neurology,Children's Hospital Affiliated of Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou,Henan 450018,China;Translational Medical Research Center Company,Beijing 100176,China;Center for Genetic Medicine,Xuzhou Maternity and Child Health Care Hospital Affiliated to Xuzhou Medical University,Xuzhou,Jiangsu 221000,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/河南省儿童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 [2]郑州大学附属儿童医院/河南省儿童医院郑州儿童医院神经内科,河南郑州450018 [3]北京智因东方转化医学研究中心有限公司,北京100176 [4]徐州医科大学附属徐州妇幼保健院遗传医学中心,江苏徐州221000

出　　处：《中国优生与遗传杂志》2024年第4期823-827,共5页Chinese Journal of Birth Health & Heredity

基　　金：国家自然科学基金青年项目(81901387);河南省科技攻关计划项目(232102311006);河南省医学科技攻关计划联合共建项目(LHGJ20210632);河南省儿童神经发育工程研究中心开放课题(SG202202);徐州市医学重点人才项目(XWRCHT20220060)。

摘　　要：目的分析Dravet综合征的临床特征以及SCN1A基因突变特点,提高对Dravet综合征的早期诊断和鉴别,避免无效治疗。方法收集郑州大学附属儿童医院1例确诊为SCN1A基因新生无义突变致Dravet综合征患儿的临床资料,取患者及其父母外周血进行Trio全外显子组测序,结合结果进行分析讨论。结果患儿为7个月25天的男童,临床表现为早期发热,后期无热性惊厥,全面性发育迟缓及局灶性癫痫发作等。实验室检查头颅磁共振未见异常,视频脑电图监测到广泛性棘慢波、多棘慢波阵发,10余次肌阵挛发作。Trio全外显子组测序结果显示患儿SCN1A基因第26外显子发生c.4486C>T(p.Q1496^(*))新生杂合无义突变,父亲和母亲基因型均为野生型。依据美国医学遗传学与基因组学学会遗传变异分类标准和指南,SCN1A基因c.4486C>T位点突变为致病性变异(PVS1+PS2+PM2+PP3)。结论SCN1A基因新发无义突变c.4486C>T可能是Dravet综合征患儿的病因,基因检测有助于Dravet综合征的早期诊断和合理治疗。Objective To analyze the clinical manifestations of Dravet syndrome and the characteristics of SCN1A gene mutation,so as to improve the early diagnosis and distinguishing of Dravet syndrome and avoid ineffective treatment.Methods The clinical data of a patient with Dravet syndrome caused by new nonsense mutation of SCN1A gene locus in the Children's Hospital Affiliated of Zhengzhou University were collected and analyzed.Trio whole exome sequencing was performed to identify pathogenic gene variants in the proband and the parents.Results The patient was a 7 months-and 25days-old boy with clinical manifestations including initial symptom of fever,and later persistent convulsion with no fever,global developmental retardation,status epilepticus,and focal epilepsy,etc.Cranial magnetic resonance imaging showed no abnormality,while long range video electroencephalogram showed more than ten myoclonic seizures of extensive spikes and slow waves in EEG of this patient.Trio whole exome sequencing revealed heterozygous nonsense mutation c.4486C>T(p.Q1496^(*))in exon 26 of SCN1A gene,while the parental genotypes were wild type.According to the American College of Medical Genetics standards and guidelines,c.4486C>T was predicted to be pathogenic(PVS1+PS2+PM2+PP3).Conclusion The novel nonsense mutation c.4486C>T in SCN1A gene probably is the underlying etiology in this patient,and genetic detection is helpful for early diagnosis and rational treatment of Dravet syndrome.

关 键 词：SCN1A基因 DRAVET综合征 基因变异 癫痫 儿童 

分 类 号：R725[医药卫生—儿科]