摘要目的 研究家族性Dravet综合征(DS)家系成员的临床表型和基因突变,为遗传咨询提供指导.方法 收集2005年2月至2016年3月在北京大学第一医院儿科门诊就诊的家族性DS家系的临床资料和外周血DNA,采用Sanger测序和多重连接依赖探针扩增技术(MLPA)筛查SCN1A基因突变;采用靶向捕获二代测序癫痫基因检测包对未发现SCN1A突变的家系进行筛查.结果 共收集6个家族性DS家系,每个家系均有2例DS受累者,其中2个家系为姐妹或姐弟同患,2个家系为母子或母女同患,1个家系为单卵双胎同患,1个家系为异卵双胎同患.6个DS家系中,5个家系发现携带SCN1A基因突变(R101Q、R377X、L390P、F1486L、R1245X),其中3个家系证实为SCN1A遗传性杂合突变,均来自母源,母亲表型为DS或热性惊厥附加症(FS+);2个家系Sanger测序结果高度怀疑父母一方可能为SCN1A突变嵌合体,携带突变的父或母表型均正常.余1个家系未发现SCN1A基因突变,送检癫痫基因检测包未发现DS其他候选基因突变,父母表型正常.结论 家族性DS可表现为患儿及父母一方同患或同胞共患,多数为SCN1A基因突变所致,少数致病基因尚未明确;家族性DS多数为遗传性突变,包括父母一方可能为突变嵌合体;携带SCN1A突变的父母一方临床表型可为DS、FS+或表型正常.

abstractsObjective To summarize the phenotype and gene mutation in familial Dravet syndrome (DS) and provide guidance for genetic counseling.Methods The clinical data and peripheral blood DNA samples of familial DS patients and their parents were collected from February 2005 to March 2016 in Department of Pediatrics,Peking University First Hospital.SCN1A mutations were screened by adopting Sanger sequencing and multiple ligation-dependent probe amplification (MLPA).Next generation sequencing(NGS) for epilepsy-related gene-panel was applied to SCN1A mutation-negative patients and their parents.Results In 6 DS families,each consisted of 2 DS patients.Two families had siblings affected,one family involved mother and son,one family involved mother and daughter,one had monozygotic twins affected and one had dizygotic twins involved.SCN1A mutations were identified in 5 DS families (R101 Q,R377X,L390P,F1486L,R1245X).Among the 5 DS families with SCN1A mutations,3 families were identified as inherited heterozygous mutations,and phenotypes of the transmitting parents were DS or febrile seizure plus (FS +).While 2 families were highly suspected of parental mosaicism from the results of Sanger sequencing,and the transmitting parents had no history of febrile and epileptic seizures.No SCN1A and other DS-related gene mutation that had been reported was found in the remaining family and the phenotype of parents were normal.Conclusions The affected members of familial DS could be exhibited as one parent and child affected,or sibling pairs,monozygotic or dizygotic twins involved.The majority of familial DS carried SCN1A mutations,while others might carry other DS-causing gene mutation.The mutations of familial DS patients were inherited from one parent,including a mosaic transmitting parent.The phenotypes of the parent carrying SCN1A mutation could be DS,FS + or normal.