Cossette Patrick, Liu Lidong, Brisebois Katéri, Dong Haiheng, Lortie Anne, Vanasse Michel, Saint-Hilaire Jean-Marc, Carmant Lionel, Verner Andrei, Lu Wei-Yang, Wang Yu Tian, Rouleau Guy A
Centre for Research in Neuroscience, McGill University Health Center Research Institute and McGill University, 1650 Cedar Avenue, Montréal, Québec H3G 1A4, Canada.
Nat Genet. 2002 Jun;31(2):184-9. doi: 10.1038/ng885. Epub 2002 May 6.
Although many genes that predispose for epilepsy in humans have been determined, those that underlie the classical syndromes of idiopathic generalized epilepsy (IGE) have yet to be identified. We report that an Ala322Asp mutation in GABRA1, encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A (GABA(A)), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABA(A) receptors that contain the mutant subunit show a lesser amplitude of GABA-activated currents in vitro, indicating that seizures may result from loss of function of this inhibitory ligand-gated channel. Our results confirm that mutation of GABRA1 predisposes towards a common idiopathic generalized epilepsy syndrome in humans.
尽管许多导致人类癫痫易感性的基因已被确定，但那些构成特发性全身性癫痫（IGE）经典综合征基础的基因尚未被识别。我们报告，在一个患有青少年肌阵挛癫痫的法裔加拿大家庭的患病个体中，发现了编码γ-氨基丁酸A型受体（GABA(A)）α1亚基的GABRA1基因中的一个Ala322Asp突变。与野生型受体相比，含有突变亚基的GABA(A)受体在体外显示出较小幅度的GABA激活电流，表明癫痫发作可能是由于这种抑制性配体门控通道功能丧失所致。我们的结果证实，GABRA1突变使人类易患一种常见的特发性全身性癫痫综合征。
