A mutation in the GABA(A) receptor alpha(1)-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.


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.
Maljevic
Snezana
S
Neurologische Klinik, Universität Ulm, Ulm, Germany.
Krampfl
Klaus
K
Cobilanschi
Joana
J
Tilgen
Nikola
N
Beyer
Susanne
S
Weber
Yvonne G
YG
Schlesinger
Friedrich
F
Ursu
Daniel
D
Melzer
Werner
W
Cossette
Patrick
P
Bufler
Johannes
J
Lerche
Holger
H
Heils
Armin
A
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
D011963:Receptors, GABA-A