title: Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies.
abstract: A few mutations in the gene encoding the gamma 2 subunit of the gamma-aminobutyric acid receptor type A (GABRG2) have been reported in various types of epilepsy. The aim of this study is to investigate the role of GABRG2 in the pathogenesis of childhood epilepsy in a large Japanese cohort. Genetic analysis of GABRG2 was performed on 140 Japanese patients with various childhood epilepsies largely including Dravet syndrome and genetic epilepsy with febrile seizures plus. The mutational analysis identified one novel missense mutation of GABRG2 (c.236A>G: p.N40S) in a patient with generalized tonic-clonic seizures (GTCS). The mutation was heterozygous and replacing a highly conserved Asn residue with a Ser. The affected amino acid was located at residue 40 of the mature GABRG2 protein, which was near the first one of two high-affinity benzodiazepine-binding domains of the gamma2 subunit (Lys-41-Trp-82). This mutation in such an important position may hamper the function of the channel and contribute to the case's pathogenesis of GTCS.
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Shi
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Huang
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishii
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Motohiro
authors.initials: M
authors.lastname: Okada
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Morita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagafuji
authors.forename: Sawa
authors.initials: S
authors.lastname: Yasumoto
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
authors.forename: Toshio
authors.initials: T
authors.lastname: Kojima
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
mesh_terms: D000595:Amino Acid Sequence; D001216:Asparagine / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004830:Epilepsy, Tonic-Clonic / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011963:Receptors, GABA-A / Q000235:genetics*; D016415:Sequence Alignment; D012694:Serine / Q000235:genetics
chemical_list: C546279:GABRG2 protein, human; D011963:Receptors, GABA-A; D012694:Serine; D001216:Asparagine