title: A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurologische Klinik, Universität Ulm, Ulm, Germany.
authors.forename: Snezana
authors.initials: S
authors.lastname: Maljevic
authors.forename: Klaus
authors.initials: K
authors.lastname: Krampfl
authors.forename: Joana
authors.initials: J
authors.lastname: Cobilanschi
authors.forename: Nikola
authors.initials: N
authors.lastname: Tilgen
authors.forename: Susanne
authors.initials: S
authors.lastname: Beyer
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Weber
authors.forename: Friedrich
authors.initials: F
authors.lastname: Schlesinger
authors.forename: Daniel
authors.initials: D
authors.lastname: Ursu
authors.forename: Werner
authors.initials: W
authors.lastname: Melzer
authors.forename: Patrick
authors.initials: P
authors.lastname: Cossette
authors.forename: Johannes
authors.initials: J
authors.lastname: Bufler
authors.forename: Holger
authors.initials: H
authors.lastname: Lerche
authors.forename: Armin
authors.initials: A
authors.lastname: Heils
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D002675:Child, Preschool; D004832:Epilepsy, Absence / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D018613:Microscopy, Confocal; D009154:Mutation; D018408:Patch-Clamp Techniques; D010375:Pedigree; D011963:Receptors, GABA-A / Q000235:genetics* / Q000502:physiology*; D014162:Transfection
chemical_list: D011963:Receptors, GABA-A