title: Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.
abstract: 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.
authors: Centre for Research in Neuroscience, McGill University Health Center Research Institute and McGill University, 1650 Cedar Avenue, Montréal, Québec H3G 1A4, Canada.
authors: Patrick
authors: P
authors: Cossette
authors: Lidong
authors: L
authors: Liu
authors: Katéri
authors: K
authors: Brisebois
authors: Haiheng
authors: H
authors: Dong
authors: Anne
authors: A
authors: Lortie
authors: Michel
authors: M
authors: Vanasse
authors: Jean-Marc
authors: JM
authors: Saint-Hilaire
authors: Lionel
authors: L
authors: Carmant
authors: Andrei
authors: A
authors: Verner
authors: Wei-Yang
authors: WY
authors: Lu
authors: Yu Tian
authors: YT
authors: Wang
authors: Guy A
authors: GA
authors: Rouleau
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004829:Epilepsy, Generalized / Q000209:etiology / Q000235:genetics; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D020190:Myoclonic Epilepsy, Juvenile / Q000209:etiology / Q000235:genetics*; D010375:Pedigree; D011963:Receptors, GABA-A / Q000235:genetics*
chemical_list: D011963:Receptors, GABA-A