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

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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.