CAJ | 학술논문

目的分析全面性癫(癎)伴热性惊厥附加症(generalized epilepsy with febrile seizures plus,GEFS+)家系的临床表型,并筛查家系钠离子通道α1亚单位基因SCN1A突变,分析GEFS+基因型与表型的相关性.方法收集先证者及其家系成员临床资料及外周血DNA,对家系受累者临床表型进行分析,并采用PCR和DNA直接测序的方法进行SCN1A基因突变筛查.结果在39个GEFS+家系中,共有196例受累者,每个家系中有2～22例受累者不等.196例受累者的临床表型包括热性惊厥( febrile seizures,FS)92例(46.9％),热性惊厥附加症(febrile seizures plus,FS+ )62例(31.6％),FS或FS+伴部分性发作12例(6.1％),无热全面强直阵挛发作(afebrile generalized tonic-clonic seizures,AGTCS) 11例(5.6％),肌阵挛失张力癫(癎)8例(4.1％),Dravet综合征2例(1.0％),儿童失神癫(癎)1例(0.5％),FS+伴肌阵挛发作1例(0.5％),AGTCS和肌阵挛发作1例(0.5％),部分性发作1例(0.5％),发作分类不能明确5例(2.6％).39个GEFS+家系中发现4个家系(1O.3％)有SCN1A基因突变,其中3例错义突变(N935H、R1O1Q、G1382R),1例碱基缺失(C373fsx378).3例有错义突变的家系表型包括FS、FS+、FS+伴部分性发作和AGTCS.截断突变位点C373fsx378的家系表型包括FS、Fs+和Dravet综合征.有错义突变R101Q的家系其先证者的母亲和有截断突变C373fsx378的家系先证者的父亲均为体细胞突变嵌合体,表型均为Fs+.结论 GEFS+家系最常见的表型为FS和FS+,最严重的表型为Dravet综合征.GEFS+家系SCN1A基因突变率约为10％,突变类型以错义突变为主,可有截断突变.GEFS+家系中少数受累成员SCN1A突变可为体细胞嵌合体,表型相对较轻.
목적 분석전면성전(간)반열성량궐부가증(generalized epilepsy with febrile seizures plus,GEFS+)가계적림상표형,병사사가계납리자통도α1아단위기인SCN1A돌변,분석GEFS+기인형여표형적상관성.방법 수집선증자급기가계성원림상자료급외주혈DNA,대가계수루자림상표형진행분석,병채용PCR화DNA직접측서적방법진행SCN1A기인돌변사사.결과 재39개GEFS+가계중,공유196례수루자,매개가계중유2～22례수루자불등.196례수루자적림상표형포괄열성량궐( febrile seizures,FS)92례(46.9％),열성량궐부가증(febrile seizures plus,FS+ )62례(31.6％),FS혹FS+반부분성발작12례(6.1％),무열전면강직진련발작(afebrile generalized tonic-clonic seizures,AGTCS) 11례(5.6％),기진련실장력전(간)8례(4.1％),Dravet종합정2례(1.0％),인동실신전(간)1례(0.5％),FS+반기진련발작1례(0.5％),AGTCS화기진련발작1례(0.5％),부분성발작1례(0.5％),발작분류불능명학5례(2.6％).39개GEFS+가계중발현4개가계(1O.3％)유SCN1A기인돌변,기중3례착의돌변(N935H、R1O1Q、G1382R),1례감기결실(C373fsx378).3례유착의돌변적가계표형포괄FS、FS+、FS+반부분성발작화AGTCS.절단돌변위점C373fsx378적가계표형포괄FS、Fs+화Dravet종합정.유착의돌변R101Q적가계기선증자적모친화유절단돌변C373fsx378적가계선증자적부친균위체세포돌변감합체,표형균위Fs+.결론 GEFS+가계최상견적표형위FS화FS+,최엄중적표형위Dravet종합정.GEFS+가계SCN1A기인돌변솔약위10％,돌변류형이착의돌변위주,가유절단돌변.GEFS+가계중소수수루성원SCN1A돌변가위체세포감합체,표형상대교경.
Objective To summarize the phenotypes and identify SCN1A mutations in families with generalized epilepsy with febrile seizures plus (GEFS + ),and analyze the genotype- phenotype correlations in GEFS+ families.Method Genomic DNA was extracted from peripheral blood lymphocytes of the proband and other available members in the GEFS + families.The phenotypes of the affected members were analyzed.The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing.Result In 39 GEFS + families,there were 196 affected members,ranging from 2 to 22 affected members in each family.Their phenotypes included febrile seizures (FS) in 92 (46.9％ ),febrile seizures plus ( FS + ) in 62 ( 31.6％ ),FS or FS+ with partial seizures in 12 ( 6.1％ ),afebrile generalized tonic-clonic seizures (AGTCS) in 11 (5.6％ ),myoclonic atonic epilepsy in 8(4.1％ ),Dravet syndrome in 2( 1.0％ ),childhood absence epilepsy in 1 (0.5％ ),FS + with myoclonic seizures in 1 (0.5％),AGTCS and myoclonic seizures in 1 (0.5％),partial seizures in 1 (0.5％),unclassified seizures in 5 (2.6％ ).Four families were found with SCN1A mutations,including three families with missense mutation (N935H,R101Q,G1382R) and one family with truncation mutation (C373fsx378).In three families with missense mutations,the phenotypes include FS,FS+,FS+ with partial seizures,and AGTCS.In one family with truncation mutation,the phenotypes included FS,FS +,and Dravet syndrome.The mother of proband in the family with missense mutation ( R101 Q) and the father of proband in the family with truncation mutation (C373fsx378) were both somatic mosaicism.Both of their phenotypes were FS+Conclusion The most common phenotypes of GEFS+ were FS and FS +,followed by the FS/FS + with partial seizures and AGTCS.The most severe phenotype was Dravet syndrome.SCN1A mutation rate in GEFS + was about 10％.Missense mutation was common in GEFS + families,few with truncation mutation.Few members of GEFS + families had somatic mosaicism of SCN1A mutations and their phenotypes were relatively mild.