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

Ann Neurol. 2006 Jun;59(6):983-7. doi: 10.1002/ana.20874.


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 GABA(A) receptor alpha(1)-subunit, and that GABRA1 mutations rarely are associated with idiopathic generalized epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Cells, Cultured
  • Child, Preschool
  • Epilepsy, Absence / genetics*
  • Epilepsy, Absence / physiopathology*
  • Female
  • Humans
  • Immunoblotting
  • Male
  • Microscopy, Confocal
  • Mutation
  • Patch-Clamp Techniques
  • Pedigree
  • Receptors, GABA-A / genetics*
  • Receptors, GABA-A / physiology*
  • Transfection


  • Receptors, GABA-A