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 γ2 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.
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Acknowledgements
We are indebted to all members of the family for their helpful cooperation in this study. We thank Ms Takako Umemoto and Hideko Takeda for formatting and typing the manuscript and Ms Minako Yonetani and Akiyo Hamachi for the technical assistance. This study was supported in part by Grants-in-Aid for Scientific Research (S) 16109006, (A) 18209035 and 21249062, Exploratory Research 1659272, and ‘High-Tech Research Center’ Project for Private Universities-matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology, 2006–2010 ‘The Research Center for the Molecular Pathomechanisms of Epilepsy, Fukuoka University’, Research Grants (19A-6) and (21B-5) for Nervous and Mental Disorders from the Ministry of Health, Labor and Welfare and the Central Research Institute of Fukuoka University and an in-house budget of RIKEN.
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Shi, X., Huang, MC., Ishii, A. et al. Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies. J Hum Genet 55, 375–378 (2010). https://doi.org/10.1038/jhg.2010.47
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DOI: https://doi.org/10.1038/jhg.2010.47
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