A mutation in the GABAA receptor α1-subunit is associated with absence epilepsy

Objective To detect mutations in GABRA1 in idiopathic generalized epilepsy. Methods GABRA1 was sequenced in 98 unrelated idiopathic generalized epilepsy patients. Patch clamping and confocal imaging was performed in transfected mammalian cells. Results 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. Interpretation 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 GABAA receptor α1‐subunit, and that GABRA1 mutations rarely are associated with idiopathic generalized epilepsy. Ann Neurol 2006;59:983–987