Macdonald Robert L., Kang Jing-Qiong, Gallagher Martin J.
Department of Neurology, Vanderbilt University, Nashville, TN 37232-8552
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-8552
Mutations in inhibitory GABA receptor subunit genes ( and have been associated with idiopathic epilepsy syndromes (IES) including childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME), pure febrile seizures (FS), generalized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS) (also known as severe myoclonic epilepsy in infancy, SMEI). These mutations are found in both translated and untranslated gene regions and have been shown to affect the GABA 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 or by inhibiting receptor trafficking. While a clear genotype/phenotype correlation has not been established, mutations of and are associated with CAE or JME while mutations and variants of and are associated with FS, FS with CAE, GEFS+, and DS.
抑制性γ-氨基丁酸（GABA）受体亚基基因突变（和）已与特发性癫痫综合征（IES）相关，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）、热性惊厥附加症伴全身性癫痫（GEFS+）和德拉韦综合征（DS）（也称为婴儿严重肌阵挛癫痫，SMEI）。这些突变存在于基因的翻译区和非翻译区，已证明通过多种机制影响GABA受体，包括改变受体功能和/或损害受体生物合成，这些机制包括降低亚基mRNA转录或稳定性、损害亚基折叠、稳定性或寡聚化，或抑制受体运输。虽然尚未建立明确的基因型/表型相关性，但和的突变与CAE或JME相关，而和的突变及变体与FS、伴有CAE的FS、GEFS+和DS相关。
