A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy.

Abstract

To detect mutations in GABRA1 in idiopathic generalized epilepsy. GABRA1 was sequenced in 98 unrelated idiopathic generalized epilepsy patients. Patch clamping and confocal imaging was performed in transfected mammalian cells. We identified the first GABRA1 mutation in a patient with childhood absence epilepsy. Functional studies showed no detectable GABA-evoked currents for the mutant, truncated receptor, which was not integrated into the surface membrane. We conclude that this de novo mutation can contribute to the cause of "sporadic" childhood absence epilepsy by a loss of function and haploinsufficiency of the GABA(A) receptor alpha(1)-subunit, and that GABRA1 mutations rarely are associated with idiopathic generalized epilepsy.