SCN1A基因变异致遗传性癫痫伴热性惊厥附加症3个家系的临床及遗传学分析  

Analysis of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus due to variants of SCN1A gene

作　　者：杨志刚[1] 王媛[1] 陈国洪 宋丽芳 马燕丽 张炜华 Yang Zhigang;Wang Yuan;Chen Guohong;Song Lifang;Ma Yanli;Zhang Weihua(Department of Neurology,Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou,Henan 450066,China)

机构地区：[1]郑州大学附属儿童医院神经内科,郑州1450066

出　　处：《中华医学遗传学杂志》2024年第3期284-288,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81901387);河南省医学科技攻关计划联合共建项目(LHGJ20190947)

摘　　要：目的探讨3个遗传性癫痫伴热性惊厥附加症(GEFS+)家系的临床及基因变异特征。方法回顾性分析2020年1月至2021年12月就诊于郑州大学附属儿童医院的3例GEFS+先证者及其家系成员的临床资料,对其进行全外显子组测序分析,并利用Sanger测序对候选变异进行验证。结果先证者1为3岁2月龄男性,表现为热性惊厥附加症,其父亲、2个姑姑、奶奶、姨奶、舅爷及外曾祖母均在1~2岁时有发热抽搐,6岁之后未再发作。先证者2为1岁4月龄男性,表现为复杂型热性惊厥,其母亲、舅舅及外祖母在5~6岁前均有发热、抽搐。先证者3为3岁11月龄男性,表现为热性惊厥附加症,其父亲、爷爷幼年均有发热、抽搐,7~8岁后未再发作。基因检测显示先证者1的SCN1A基因存在父源c.1613T>C杂合变异,先证者2的SCN1A基因存在母源c.2804A>G杂合变异,先证者3的SCN1A基因存在父源c.1271T>C杂合变异,上述变异均被评级为可能致病性变异(PM1+PM2_Supporting+PP1+PP3+PP4)。结论SCN1A基因c.1613T>C、c.2804A>G及c.1271T>C变异考虑为3个GEFS+家系的遗传学病因。Objective To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus(GEFS+).Methods Three GEFS+probands and their pedigree members presented at the Children′s Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects.Clinical data of the pedigrees were collected.Whole exome sequencing was carried out for the probands,and Sanger sequencing was used to verify the candidate variants.Results Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus.His father,two aunts,grandmother,aunt grandmother,uncle grandfather,and paternal great-grandmother also had onset of febrile seizures at 1~2 years of age with remission before 6 years old.Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure.His mother,maternal uncle,and maternal grandmother also had febrile seizures before 5~6 years of age.Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus.His father and grandfather also had febrile seizures plus with remission at 7~8 years of age.Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A:c.1613T>C variant,proband 2 had harbored a maternally derived heterozygous SCN1A:c.2804A>G variant,and proband 3 had harbored a paternally derived heterozygous SCN1A:c.1271T>C variant.All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics(PM1+PM2_Supporting+PP1+PP3+PP4).Conclusion The c.1613T>C,c.2804A>G and c.1271T>C variants probably underlay the pathogenesis of GEFS+in these pedigrees.

关 键 词：癫痫 遗传性癫痫伴热性惊厥附加症 SCN1A基因 基因变异 

分 类 号：R742.1[医药卫生—神经病学与精神病学]