Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies
Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies
复制标题
DOI：
10.1038/jhg.2010.47
复制
发表时间：
2010-06-01
影响因子：
3.5
通讯作者：
Hirose, Shinichi
中科院分区：
文献类型：
--
作者：
Shi, XiuYu;Huang, Ming-Chih;Hirose, Shinichi
在各种类型的癫痫中已经报道了编码γ-氨基丁酸受体A型（GABRG 2）的γ 2亚基的基因中的一些突变。本研究的目的是在一个大型的日本队列中调查GABRG 2在儿童癫痫发病机制中的作用。对140名患有各种儿童癫痫的日本患者进行了GABRG 2的遗传分析，主要包括Dravet综合征和遗传性癫痫伴热性惊厥。突变分析鉴定了一例全身性强直阵挛发作（GTCS）患者中GABRG 2的一种新错义突变（c.236A > G：p.N40S）。该突变为杂合子，用Ser取代了高度保守的Asn残基。受影响的氨基酸位于成熟GABRG 2蛋白的残基40处，该残基靠近γ 2亚基（Lys-41-Trp-82）的两个高亲和力苯二氮卓结合域中的第一个。这种重要位置的突变可能会妨碍通道的功能，并有助于病例的GTCS发病机制。Journal of Human Genetics（2010）55，375-378; doi：10.1038/jhg.2010.47; 2010年5月20日在线发表
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 gamma 2 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. Journal of Human Genetics (2010) 55, 375-378; doi:10.1038/jhg.2010.47; published online 20 May 2010