婴儿严重肌阵挛癫痫钠离子通道SCNIA基因突变分析

目的 研究婴儿严重肌阵挛癫痫(severe myoclonic epilepsy of infancy,SMEI)患儿钠离子通道a1亚单位基因(sodium channel al subunit gene,SCNIA)突变筛查及遗传特征.方法 收集SMEI患儿23例及其家系成员的临床资料及外周血DNA,采用PCR扩增和DNA直接测序的方法筛查SCNIA基因的26个外显子的突变.结果 23例SMEI患儿中17例有SCNlA基因突变.基因突变率约为73.9%(17/23),其中8例为错义突变(F90S、I91T、A239T、W952G、T1210K,V1335M、V1390M、G1433E),3例为无义突变(R612X、W768X、w1408X),3例为缺失突变(A395fsX400、L556fsX557、V1778fsX1800),1例为插入突变(Y1241fsX1270),1例为剪切部位突变(IVS10+3A>G),1例为同义突变(K1492K),截断突变约占总突变的47.1%(8/17).13个突变位点(F90S、I91T、T1210K、V1335M、G1433E、R612X、W768X,A395faX400、L556fsx557、V1778fsXl800、Y1241fsXl270、IVS10+3A>G、K1492K)经相关检索未见报道.14例突变已证实为新生突变,其余3例突变尚不能确定突变来源.结论 SCNIA基因是SMEI患儿的主要致病基因,约一半为截断突变.SMEI患儿的SCNIA基因突变无热点,且多为新生突变.

Mutation analysis of the SCNIA gene in severe myoclonic epilepsy of infancy

Objective To investigate the mutations of the sodium channel α1 subunit gene (SCNIA) in severe myoelonie epilepsy of infancy (SMEI) patients and analyze its inheritance. Methods Twenty-three patients consistent with the diagnosis of SMEI were selected for SCNIA mutation analysis. Genomic DNA was extracted from peripheral blood lymphoeytes of these patients and their parents. All the twenty-six exons of the SCNIA gene were amplified by PCR and sequenced. Results In the 23 SMEI patients, 17 mutations were identified in 17 unrelated SMEI patients. The SCNIA mutation rate was 73.9 % (17/23). The mutations included 8 missense mutations (F90S, I91T, A239T, W952G, T1210K, V1335M, V1390M and G1433E), 3 nonsense mutations (R612X, W768X and W1408X), 3 deletion mutations (A395fsX400, LS56fsX557 and V1778fsX1800), 1 insertion mutation (Y1241fsX1270), 1 splice-site mutation (IVS10+3A> G) and 1 synonymous mutation (K1492K), of which 47.1% (8/17)were truncation mutations. Thirteen mutations (F90S, I91T, T1210K, V1335M, G1433E, R612X, W768X, A395fsX400, L556fsX557, V1778fsX1800, Y1241fsX1270,IVS10+3A>G and K1492K) have not been reported previously. Except for F90S, L556fsX557 and V1778fsX1800, the other 14 mutations were de novo. Condusion SCNIA is a major pathogenic gene for SMEI. About a half of the SCN1A mutations in SMEI cause truncation. There were no "hotspots" of SCN1A mutations in SMEI patients, and most mutations were de novo.