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A mutation in the GABA A receptor α 1 ‐subunit is associated with absence epilepsy
Author(s) -
Maljevic Snezana,
Krampfl Klaus,
Cobilanschi Joana,
Tilgen Nikola,
Beyer Susanne,
Weber Yvonne G.,
Schlesinger Friedrich,
Ursu Daniel,
Melzer Werner,
Cossette Patrick,
Bufler Johannes,
Lerche Holger,
Heils Armin
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20874
Subject(s) - haploinsufficiency , epilepsy , childhood absence epilepsy , mutation , generalized epilepsy , mutant , protein subunit , biology , receptor , medicine , neuroscience , genetics , phenotype , gene
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. 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 α 1 ‐subunit, and that GABRA1 mutations rarely are associated with idiopathic generalized epilepsy. Ann Neurol 2006;59:983–987