Nature Genetics31, 184 - 189 (2002)
Published online: 6 May 2002; | doi:10.1038/ng885
Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy
Patrick Cossette1, 5, Lidong Liu2, Katéri Brisebois1, Haiheng Dong3, Anne Lortie4, Michel Vanasse4, Jean-Marc Saint-Hilaire5, Lionel Carmant4, 5, Andrei Verner6, Wei-Yang Lu3, Yu Tian Wang2
& Guy A. Rouleau1
1
Centre for Research in Neuroscience, McGill University Health Center Research Institute and McGill University, 1650 Cedar Avenue, Montréal, Québec H3G 1A4, Canada.
2
Program in Brain and Behaviour, Hospital for Sick Children, Toronto, Ontario, Canada, and Department of Medicine and Brain Research Centre, Vancouver Hospital, University of British Columbia, Vancouver, Canada.
3
Neuroscience Research at Sunnybrook and Women's College Health Sciences Centre, and Departments of Anesthesia and Physiology, University of Toronto, Canada.
4
Service de Neurologie, Hôpital Sainte-Justine, Montréal, Québec, Canada.
5
Service de Neurologie, Centre Hospitalier de l'Université de Montréal—Hôpital Notre-Dame, Montréal, Québec, Canada.
6
Montreal Genome Center, The Montreal General Hospital, McGill University, Montréal, Québec, Canada.
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 1 subunit of the -aminobutyric acid receptor subtype A (GABAA), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABAA 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.
1 subunit of the 
-aminobutyric acid receptor subtype A (GABAA), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABAA 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.
