A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions
A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions
复制标题
DOI：
10.1001/archneur.59.7.1137
复制
发表时间：
2002-07-01
影响因子：
--
通讯作者：
Steinlein, OK
中科院分区：
文献类型：
--
作者：
Kananura, C;Haug, K;Steinlein, OK
背景：最近在2个特发性癫痫家系中发现了GABRG2基因的错义突变，该基因编码中枢神经系统γ-氨基丁酸(GABA)受体的Gamma2亚单位。目的：探讨GABRG2基因在特发性失神癫痫遗传易感性中的作用。设计：通过单链构象分析筛选GABRG2基因突变。结果：发现一个IVS6+2T-->；G点突变导致内含子6剪接供体位点突变。据预测，这种突变会导致一种不起作用的蛋白质，在一个患有儿童期缺席癫痫和热性惊厥的家庭中，这种突变与疾病状态有关。关联研究没有发现特发性失神癫痫患者和对照组(P>；.35)常见外显子5多态(C588T)的等位基因和基因型频率有任何显著差异。结论：我们的研究发现了一个剪接供体突变，可能导致了一个不起作用的GABRG2亚单位。这种突变发生在单个核心家庭中受影响的成员的杂合性，表现出儿童失神癫痫和发热性惊厥的表型谱。GABRG2基因似乎对常见的特发性失神癫痫综合征具有罕见而不是常见的主要易感性效应。
Context: Missense mutations in the GABRG2 gene, which encodes the gamma2 subunit of central nervous gamma-aminobutyric acid (GABA), receptors, have recently been described in 2 families with idiopathic epilepsy. In one of these families, the affected individuals predominantly exhibited childhood absence epilepsy and febrile convulsions.Objective: To assess the role of GABRG2 in the genetic predisposition to idiopathic absence epilepsies.Design: The GABRG2 gene was screened by single-strand conformation analysis for mutations. Furthermore, a population-based association study assessing a common exon 5 polymorphism (C588T) was carried out.Patients: The sample was composed of 135 patients with idiopathic absence epilepsy and 154 unrelated and ethnically matched controls.Results: A point mutation (IVS6 + 2T-->G) leading to a splice-donor site mutation in intron 6 was found. The mutation, which is predicted to lead to a nonfunctional protein, cosegregates with the disease status in a family with childhood absence epilepsy and febrile convulsions. The association study did not find any significant differences in the allele and genotype frequencies of the common exon 5 polymorphism (C588T) between patients with idiopathic absence epilepsy and controls (P>.35).Conclusions: Our study identified a splice-donor-site mutation that was probably causing a nonfunctional GABRG2 subunit. This mutation occurred in heterozygosity in the affected members of a single nuclear family, exhibiting a phenotypic spectrum of childhood absence epilepsy and febrile convulsions. The GABRG2 gene seems to confer a rare rather than a frequent major susceptibility effect to common idiopathic absence epilepsy syndromes.