3P135 Mutation analysis of the Na+ channel and GABAA receptor genes in individuals with frequent febrile seizures or febrile seizures plus

• Published in: Journal of Pharmacological Sciences 2003, Vol.91 (suppl.1), p.235-235
• Main Authors: Akira Kohashi, Goryu Fukuma, Atsushi Ishii, Ryo Saito, Kenji Honda, Yukio Takano, Akihisa Mitsudome, Shinichi Hirose
• Format: Article
• Language: Japanese
• ISSN: 1347-8613

The exact molecular mechanisms of febrile seizures (FS) have yet to be elucidated. Genetic defects have been identified in ADEFS+, a familial epilepsy phenotype considered as a clinical subset of FS. FS plus (FS+) is a phenotype where affected individuals have FS extending beyond 6 years of age, with or without various afebrile seizures and is a feature in ADEFS+. The underlying mutations were found in genes encoding several Na+ channel subunits and the γ2 subunit of GABAA receptors in the brain. This line of evidence suggests the involvement of such genes in the pathogenesis of frequent FS and FS+. To test this hypothesis, genetic analyses were done for individuals with frequent FS or FS+. The subjects included 55 individuals with FS 3 times or more and 29 with FS+. As a control, 96 healthy volunteers were also recruited. Genetic abnormalities of the genes encoding α1, α2, β1 and β2 subunits of Na+ channel and α1, β2 and γ2 subunits of GABAA receptor were sought in genomic DNA using a direct sequencing method. A missense of the GABAA receptor α1 subunit gene was found in a proband with FS+ and the healthy farther. Otherwise, no mutation was found in the rest within the regions examined. Abnormahties of Nat channels and GABAA receptors may not be the major cause of FS and FS+.