Major advances in the identification of genes implicated in idiopathic epilepsy have been made. Generalized epilepsy with febrile seizures plus (GEFS+), benign familial neonatal convulsions and nocturnal frontal lobe epilepsy, three autosomal dominant idiopathic epilepsies, result from mutations affecting voltage-gated sodium and potassium channels, and nicotinic acetylcholine receptors, respectively 1, 2, 3, 4, 5, 6. Disruption of GABAergic neurotransmission mediated by γ-aminobutyric acid (GABA) has been implicated in epilepsy for many decades 7. We now report a K289M mutation in the GABA A receptor γ2-subunit gene (GABRG2) that segregates in a family with a phenotype closely related to GEFS+(ref. 8), an autosomal dominant disorder associating febrile seizures and generalized epilepsy previously linked to mutations in sodium channel genes 1, 2. The K289M mutation affects a highly conserved residue located in the extracellular loop between transmembrane segments M2 and M3. Analysis of the mutated and wild-type alleles in Xenopus laevis oocytes confirmed the predicted effect of the mutation, a decrease in the amplitude of GABA-activated currents. We thus provide the first genetic evidence that a GABA A receptor is directly involved in human idiopathic epilepsy.