上海市崇明县热性惊厥与SCN1A基因热点多态性变异的相关性分析
Analysis of the correlation between febrile seizure and hot-spot polymorphism variation in SCN1A gene in children from Chongming County, Shanghai

目的 ·了解上海市崇明县儿童热性惊厥（FS）与电压门控钠离子通道α1亚型（SCN1A）基因外显子25、26及3’UTR区域之间的相关性。方法 ·提取96例FS患儿[包括32例全面性癫痫伴热性惊厥附加症（GEFS+）患儿]和53例健康对照组儿童的外周静脉血基因组DNA，进行SCN1A基因E25、E26及3’UTR区域PCR扩增及测序分析。结果 ·病例组和对照组SCN1A基因E25、E26均未见突变。 3’UTR区域1例GEFS+患儿存在c.310-311delGT变异，2例FS患儿存在c.589T>G变异，6例存在c.593T>G变异；对照组均未发现变异。病例组和对照组已报道的单核苷酸多态性（SNP）c.1025T>C发生频率分别为18.2%和24.5%，2组间差异无统计学意义。预测结果显示114种miRNA能与SCN1A基因3’UTR区结合。c.310-311delGT不位于miRNA与SCN1A基因3’UTR区的结合序列内，c.589T>G变异、c.589T>G变异均位于此序列中。结论 ·经检测SCN1A基因E25、E26均未见突变；3’UTR区域发现c.310-311delGT、c.589T>G和c.593T>G变异；SNPc.1025T >C与FS无明显关联。
： Objective · To explore the correlation of febrile seizure (FS) with voltage-gated sodium channel alpha 1 subtype (SCN1A) gene exons 25, 26 and 3’UTR region in children from Shanghai chongming County. Methods · The genomic DNA in peripheral venous blood was extracted from 96 children with FS (including 32 cases of genetic epilepsy with febrile seizures plus [GEFS+]) and 53 healthy controls. PCR amplification and sequencing analysis were performed for SCN1A gene exons 25, 26 and 3’UTR region. Results · No mutation in SCN1A gene exons E25, E26 was found in both groups. For 3’UTR region, c.310311 delgt GT variation was found in 1 case of GEFS+, c.589 T> G variation in 2 cases of FS, and c.593 T>G variation in 6 cases, while no mutation was found in the control group. Reported frequencies of single nucleotide polymorphism (SNP) c.1025T>C were 18.2% (the case group) and 24.5% (the control group). The difference between two groups was not statistically significant. Prediction results showed that 114 microRNAs could bind with the 3’UTR region of SCN1A gene. C.310-311 delGT was not located in the sequence where miRNAs bound with 3’UTR region of SCN1A gene, while c. 589 T>G and c.593 T > G variations were located in this sequence. Conclusion · No mutation was found in SCN1Agene exons E25, E26. The c. 310-311delGT, c.589 T > G, and c. 593 T > G variations were found in 3’UTR region. There is no obvious correlation between SNPc.1025T>C and FS