Identification of the responsible genes for child epilepsy targeting abnormalities in the pore region of ion channels expressed in the central nerve system

通过对中枢神经系统离子通道编码基因突变的基因分析，我们有以下发现：所使用的标本保存在银行中，保存着从各种癫痫综合征患者身上获得的DNA样本。在广泛性癫痫伴热性发作+ (GEFS+)患者中，在编码Na+通道a1亚基的基因SCN1A中发现了两个新的突变。此外，我们发现编码Na+通道a2亚基的基因SCN2A与常染色体显性癫痫伴发热性癫痫发作相关。突变导致通道功能的缓慢失活，从而导致通道的超不可模仿性。在婴儿期患有严重肌阵挛性癫痫的日本患者中也发现了一些SCN1A突变。我们已经做了平行的研究，在体外系统和转基因动物中也产生了含有上述系列研究中发现的突变的通道功能。

We have made the following discoveries based on the genetic analyses searching mutations of genes encoding ion channels expressed in the central nerve system. The specimens used were in the bank holding DNA samples obtained from patients with various epilepsy syndrome. Two novel mutations have been identified in the gene encoding a1 subunit of Na+ channel, SCN1A in patients with generalized epilepsy with febrile seizures plus (GEFS+). Furthermore, we found that the gene encoding a2 subunit of Na+ channel, SCN2A is associated with autosomal dominant epilepsy with febrile seizures plus. The mutation result in slow inactivation in the channel function thereby cause hyper inimitability of the channel. A number of mutations of SCN1A were also identified in Japanese patients with severe myoclonic epilepsy in infancy. We have done parallel studies where channel function harboring the mutations identified in the above series of study in in vitro system and transgenic animals were also generated.