γ-氨基丁酸A（GABA(A)）受体α1亚基的突变与失神癫痫有关。
A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy.
作者信息
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
机构信息
Neurologische Klinik, Universität Ulm, Ulm, Germany.
出版信息
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.
目的
检测特发性全身性癫痫患者中GABRA1基因的突变情况。
方法
对98例无亲缘关系的特发性全身性癫痫患者的GABRA1基因进行测序。在转染的哺乳动物细胞中进行膜片钳和共聚焦成像实验。
结果
我们在一名儿童失神癫痫患者中鉴定出首个GABRA1基因突变。功能研究表明，该突变的截短型受体未整合到细胞膜表面，未检测到γ-氨基丁酸（GABA）诱发的电流。
解读
我们得出结论，这种新发突变可通过γ-氨基丁酸A（GABA(A)）受体α(1)亚基的功能丧失和单倍剂量不足导致“散发性”儿童失神癫痫的发生，且GABRA1基因突变很少与特发性全身性癫痫相关。
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