A KV4.2 truncation mutation in a patient with temporal lobe epilepsy
A KV4.2 truncation mutation in a patient with temporal lobe epilepsy
复制标题
DOI：
10.1016/j.nbd.2006.07.001
复制
发表时间：
2006-11-01
影响因子：
6.1
通讯作者：
Yamakawa, Kazuhiro
中科院分区：
文献类型：
--
作者：
Singh, Baljinder;Ogiwara, Ikuo;Yamakawa, Kazuhiro
颞叶癫痫（TLE）具有多因素病因学，涉及发育、环境和遗传成分。在这里，我们报告了一个TLE患者中发现的电压门控钾通道基因突变，即K（v）4.2截短突变。由A 'CND 2基因编码的K（v）4.2通道介导脑中的A电流。鉴定的突变对应于N587 fsX 1氨基酸变化，预测产生在羧基末端缺少最后44个氨基酸的截短的K（v）4.2蛋白。电生理学分析表明，在表达该K（v）4.2-N587 fsX 1 μ m通道的细胞中，K+电流密度减弱，这与TLE的异常神经元兴奋性模型一致。我们的观察，连同其他证据，提出了KCjVD 2在TLE病因学中的作用的有趣的可能性。(c)2006年爱思唯尔公司All rights reserved.
Temporal lobe epilepsy (TLE) has a multifactorial etiology involving developmental, environmental, and genetic components. Here, we report a voltage-gated potassium channel gene mutation found in a TLE patient, namely a K(v)4.2 truncation mutation. K(v)4.2 channels, encoded by the A'CND2 gene, mediate A currents in the brain. The identified mutation corresponds to an N587fsX1 amino acid change, predicted to produce a truncated K(v)4.2 protein lacking the last 44 amino acids in the carboxyl terminal. Electrophysiological analysis indicates attenuated K+ current density in cells expressing this K(v)4.2-N587fsX1 mutantchannel, which is consistent with a model ofaberrant neuronal excitabilit, * v characteristic of TLE. Our observations, together with other lines ofevidence, raise the intriguing possibility of a role for KCjVD2 in the etiology of TLE. (c) 2006 Elsevier Inc. All rights reserved.