全面性癫痫伴热性惊厥附加症的临床表型和SCN1A基因筛查研究  

Clinical analysis and screening for SCNIA gene mutation in two pedigrees of generalized epilepsies with febrile seizures plus

作　　者：王新华[1] 周水珍[1] 郭倩[1] 孙道开[1] 

机构地区：[1]复旦大学附属儿科医院神经内科,上海201102

出　　处：《中华儿科杂志》2009年第8期570-574,共5页Chinese Journal of Pediatrics

摘　　要：目的分析全面性癫疴伴热性惊厥附加症（generaliz edepilepsies with febrile seizures plus，GEFS^＋）的临床特点，并对部分患者进行SCN1A基因筛查，寻找基因突变。方法收集两个GEFS^＋家系的临床资料，并进行分析；留取先证者和部分家系成员的血液标本，通过变性高效液相色谱法（denaturing high performance liquid chromatography，DHPLC）等方法进行SCN1A基因筛查、测序及序列分析。结果（1）两个家系共101名成员，其中受累者28例（男、女各14例）。发作表型有热性惊厥（FS）7例、热性惊厥附加症（FS^＋）6例、FS^＋伴失神发作1例、FS^＋伴肌阵挛发作1例。未发现严重发作表型。另外，有肯定的临床发作，但由于不能获得详细的临床资料而不能进行发作分类者13例；两个家系都符合常染色体显性遗传，其中一个家系存在双系遗传现象。（2）GEFS^＋家系B的先证者和家系正常对照均发现SCN1A第9外显子存在A〉G突变（c．1212A〉G），系一多态性位点；SCN1A其余外显子未发现突变。结论本研究在GEFS^＋家系B仅发现G／A多态现象，未发现SCN1A致病性突变，支持其遗传异质性；病因学有待进一步研究。Objective To study the clinical and genetic characteristics of generalized epilepsy with febrile seizures plus （ GEFS ^＋ ）. Methods Data of two probands of the disease were collected through outpatient clinic. DNA was extracted from peripheral blood leukocytes using RelaxGene Blood DNA System. Twenty-six exons of SCN1A were amplified by polymerase chain reaction （ PCR）, the PCR products were screened by denaturing high performance liquid chromatography （ DHPLC）, then the abnormal fragments were sequenced by Sanger method in order to find the mutations of SCN1A gene. Results （ 1 ） There were 28 affected individuals in the two families of GEFS ^＋ （14 males and 14 females）. Febrile seizures （FS） were present in 7 cases, febrile seizures plus （ FS ^＋ ） in 6 cases, FS ^＋ and absence seizures in 1 case, FS ^＋ and myoclonic seizures in 1 case, uncertain type in 13 cases. No severe phenotype was seen. Bilineal inheritance occured in one GEFS^＋ family. （2） A samesense mutation （c. 1212A 〉 G） of SCN1A gene was found in the proband and an unaffected individual of pedigree B of GEFS^＋. Conclusions （ 1 ） GEFS ^＋ is a syndrome with the characteristics of heterogeneous clinical phenotypes; bilineal inheritance suggests the possibility of complex inheritance with additive gene effects. （2） Our study failed to provide evidence supporting a causal relation between the SCN1A mutation and the etiologic gene in the GEFS ^＋ family B, which indicates that GEFS ^＋ has the phenotypic and geuotypic heterogeneity.

关 键 词：癫痫 全面性 惊厥 发热性 系谱 基因 遗传 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R556.61[医药卫生—临床医学]