摘要目的 分析全面性癫(癎)伴热性惊厥附加症(generalized epilepsies with febrile seizures plus,GEFS+)的临床特点,并对部分患者进行SCNIA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 hish performance liquid chromatography,DHPLC)等方法进行SCNIA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.

abstractsObjective 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 myoclonie seizures in 1 case, uncertain type in 13 cases. No severe phenotype was seen. Bilineal inheritance occurred in one GEFS+ family. (2) A samesense mutation (c. 1212A >G) of SCNI1A 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 genotypic heterogeneity.