Sodium channel α1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms
Sodium channel α1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms
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DOI：
10.1212/01.wnl.0000086379.71183.78
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发表时间：
2003-09-23
期刊：
影响因子：
9.9
通讯作者：
Scheffer, IE
中科院分区：
文献类型：
--
作者：
Wallace, RH;Hodgson, BL;Scheffer, IE
背景资料：SCN1A是编码钠通道α 1亚基的基因，在婴儿严重肌阵挛性癫痫（SMEI）和全身性癫痫伴热性惊厥加重（GEFS（+））中发现了突变。SMEI中的突变包括错义突变、无义突变和移码突变，这些突变在受影响的患者中更常见。这一发现很难与大部分SMEI患者的GEFS（+）家族史相一致。婴儿痉挛（IS）或West综合征是一种通常有症状的严重癫痫性脑病。在某些情况下，没有发现病因，并且有癫痫家族史。方法：对24例SMEI和23例IS患者进行SCN1A检测。结果：24例SMEI患者中有8例（33%）发现突变，频率远低于欧洲和日本的初始报告。在IS患者中鉴定了羧基末端附近的一个突变。在24例SMEI患者中，17例有癫痫发作家族史。结论：SMEI患者SCN1A突变率表明其他因素可能在SMEI中起重要作用。与GEFS（+）相关的不太严重的突变可能与其他基因座相互作用，在有GEFS（+）家族史的病例中引起SMEI。这项研究扩展了SCN1A突变的表型异质性，包括IS。
Background: Mutations in SCN1A, the gene encoding the alpha1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS(+)). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS(+) in a significant proportion of patients with SMEI Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy. Method: The authors screened SCN1A in 24 patients with SMEI and 23 with IS. Results: Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI. Conclusions: The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS(+) could interact with other loci to cause SMEI in cases with a family history of GEFS(+). This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.