Dysfunction of Na+ Channel with a Mutation Identified in Epilepsy Patients Laboratory for Neurogenetics Laboratory for Memory and Learning The Laboratory for Neurogenetics and the Laboratory for Memory and Learning, in collaboration with the School of Medicine at Fukuoka University have discovered a mutation in the Na+ channel subunit gene in patients with epilepsy, and clarified that the channel protein with this mutation exhibits dysfunctions. Most types of epilepsy involve genetic background, and the number of genes responsible for epilepsy can be more than one thousand. However, only 25 genes have been identified to date due to the complex inheritance pattern of epilepsy. There are two types of epilepsy: one is idiopathic epilepsy, which shows epileptic seizures as disease phenotypes, and the other is symptomatic epilepsy which is more serious and involves symptoms such as ataxia and dementia. Our research groups investigated and analyzed 19 family lines with idiopathic epilepsy, focusing on the Na+ channel genes that control the activities of neurons. As a result, we discovered a mutation (R188W) in the subunit gene, which involved a change of the 188th amino acid from arginine (Arg) to tryptophan (Trp) (Fig.1). The R188 amino acid was highly conserved among the a-subunit members and the mutation was observed only in epilepsy patients. Furthermore, we confirmed that the channel protein with this mutation exhibits electrophysiologic abnormalities that are similar to those of the Na+ channel protein observed in patients with cardiovascular disease and myopathy (Fig.2). These results demonstrated for the first time the possibility that an abnormality of the Na+ channel subunit gene results in a specific type of epilepsy. The results obtained will greatly contribute to the future development and improvement of diagnostic methods and therapies for epilepsy. 　 Sugawara, T., Tsurubuchi, Y., Agarwala, K.L., Ito, M., Fukuma, G., Mazaki-Miyazaki, E., Nagafuji, H., Noda, M., Imoto, K., Wada, K., Mitsudome, A., Kaneko, S., Montal, M., Nagata, K., Hirose, S., Yamakawa, K. (2001) A missense mutation of the Na+ channel aII subunit gene Nav1.2 in a patient with febrile and afebrile seizures causes channel dysfunction. Proc. Natl. Acad. Sci. USA 98: 6384-6389.