Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies.
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.
Shi
Xiuyu
X
Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.
Huang
Ming-Chih
MC
Ishii
Atsushi
A
Yoshida
Shuichi
S
Okada
Motohiro
M
Morita
Kohtaro
K
Nagafuji
Hiroshi
H
Yasumoto
Sawa
S
Kaneko
Sunao
S
Kojima
Toshio
T
Hirose
Shinichi
S
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
C546279:GABRG2 protein, human; D011963:Receptors, GABA-A; D012694:Serine; D001216:Asparagine