Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy

被引：446

作者：

Cossette, P

Liu, LD

Brisebois, K

Dong, HH

Lortie, A

Vanasse, M

Saint-Hilaire, JM

Carmant, L

Verner, A

Lu, WY

Wang, YT

Rouleau, GA

机构：

[1] McGill Univ, Ctr Hlth, Inst Res, Neurosci Res Ctr, Montreal, PQ H3G 1A4, Canada

[2] Hosp Sick Children, Program Brain & Behav, Toronto, ON M5G 1X8, Canada

[3] Univ British Columbia, Vancouver Hosp, Res Ctr, Dept Med & Brain, Vancouver, BC, Canada

[4] Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Toronto, ON, Canada

[5] Univ Toronto, Dept Anesthesia, Toronto, ON, Canada

[6] Univ Toronto, Dept Physiol, Toronto, ON, Canada

[7] Hop St Justine, Neurol Serv, Montreal, PQ, Canada

[8] Univ Montreal, Ctr Hosp, Hop Notre Dame, Serv Neurol, Montreal, PQ, Canada

[9] McGill Univ, Montreal Gen Hosp, Montreal Genome Ctr, Montreal, PQ, Canada

来源：

NATURE GENETICS | 2002年 / 31卷 / 02期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1038/ng885

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：184 / 189

页数：6

共 30 条

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