Sugawara Takashi, Tsurubuchi Yuji, Fujiwara Tateki, Mazaki-Miyazaki Emi, Nagata Keiichi, Montal Mauricio, Inoue Yushi, Yamakawa Kazuhiro
Laboratory for Neurogenetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Epilepsy Res. 2003 May;54(2-3):201-7. doi: 10.1016/s0920-1211(03)00084-6.
Severe myoclonic epilepsy in infancy (SMEI) is characterized by intractable febrile and afebrile seizures, severe mental decline, and onset during the first year of life. Nonsense, frameshift, and missense mutations of SCN1A gene encoding the voltage-gated Na(+) channel alpha-subunit type I (Na(v)1.1) have been identified in patients with SMEI. Here, we performed whole-cell patch-clamp analyses on HEK293 cells expressing human Na(v)1.1 channels bearing SMEI nonsense and missense mutations. The mutant channels showed remarkably attenuated or barely detectable inward sodium currents. Our findings indicate that SMEI mutations lead to loss-of-function and may contribute to the development of SMEI phenotypes.
婴儿严重肌阵挛性癫痫（SMEI）的特征为顽固性热性和无热惊厥、严重智力衰退，且发病于生命的第一年。在SMEI患者中已鉴定出编码电压门控钠通道α亚基I型（Na(v)1.1）的SCN1A基因存在无义、移码和错义突变。在此，我们对表达带有SMEI无义及错义突变的人Na(v)1.1通道的HEK293细胞进行了全细胞膜片钳分析。突变通道显示出明显减弱或几乎检测不到的内向钠电流。我们的研究结果表明，SMEI突变导致功能丧失，并可能促成SMEI表型的发展。
