Singh Baljinder, Ogiwara Ikuo, Kaneda Makoto, Tokonami Natsuko, Mazaki Emi, Baba Koichi, Matsuda Kazumi, Inoue Yushi, Yamakawa Kazuhiro
Laboratory for Neurogenetics, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
Neurobiol Dis. 2006 Nov;24(2):245-53. doi: 10.1016/j.nbd.2006.07.001. Epub 2006 Aug 24.
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 Kv4.2 truncation mutation. Kv4.2 channels, encoded by the KCND2 gene, mediate A currents in the brain. The identified mutation corresponds to an N587fsX1 amino acid change, predicted to produce a truncated Kv4.2 protein lacking the last 44 amino acids in the carboxyl terminal. Electrophysiological analysis indicates attenuated K+ current density in cells expressing this Kv4.2-N587fsX1 mutant channel, which is consistent with a model of aberrant neuronal excitability characteristic of TLE. Our observations, together with other lines of evidence, raise the intriguing possibility of a role for KCND2 in the etiology of TLE.
颞叶癫痫（TLE）病因多因素，涉及发育、环境和遗传因素。在此，我们报告在一名TLE患者中发现的电压门控钾通道基因突变，即Kv4.2截短突变。由KCND2基因编码的Kv4.2通道介导大脑中的A电流。鉴定出的突变对应于N587fsX1氨基酸变化，预计会产生一种截短的Kv4.2蛋白，其羧基末端缺少最后44个氨基酸。电生理分析表明，表达这种Kv4.2-N587fsX1突变通道的细胞中K+电流密度减弱，这与TLE异常神经元兴奋性模型一致。我们的观察结果与其他证据一起，提出了KCND2在TLE病因中起作用的有趣可能性。
