Department of Neurology, Vanderbilt University, 6140 Medical Research Building III, 465 21st Avenue, Nashville, TN 37232-8552, USA.
J Physiol. 2010 Jun 1;588(Pt 11):1861-9. doi: 10.1113/jphysiol.2010.186999. Epub 2010 Mar 22.
Mutations in inhibitory GABAA receptor subunit genes (GABRA1, GABRB3, GABRG2 and GABRD) have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME), pure febrile seizures (FS), generalized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS)/severe myoclonic epilepsy in infancy (SMEI). These mutations are found in both translated and untranslated gene regions and have been shown to affect the GABAA receptors by altering receptor function and/or by impairing receptor biogenesis by multiple mechanisms including reducing subunit mRNA transcription or stability, impairing subunit folding, stability, or oligomerization and by inhibiting receptor trafficking.
抑制性 GABAA 受体亚基基因(GABRA1、GABRB3、GABRG2 和 GABRD)的突变与遗传性癫痫综合征有关,包括儿童失神癫痫(CAE)、青少年肌阵挛癫痫(JME)、单纯热性惊厥(FS)、热性惊厥附加全身性癫痫(GEFS+)和 Dravet 综合征(DS)/婴儿严重肌阵挛性癫痫(SMEI)。这些突变存在于翻译和非翻译基因区域,已经通过多种机制被证明会影响 GABAA 受体,包括降低亚基 mRNA 转录或稳定性、损害亚基折叠、稳定性或寡聚化,以及抑制受体运输。