Dept. of Medicine and Health Science, University of Molise, Campobasso, Italy.
Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Pharmacol Res. 2020 Oct;160:105200. doi: 10.1016/j.phrs.2020.105200. Epub 2020 Sep 15.
De novo variants in KCNQ2 encoding for Kv7.2 voltage-dependent neuronal potassium (K) channel subunits are associated with developmental epileptic encephalopathy (DEE). We herein describe the clinical and electroencephalographic (EEG) features of a child with early-onset DEE caused by the novel KCNQ2 p.G310S variant. In vitro experiments demonstrated that the mutation induces loss-of-function effects on the currents produced by channels incorporating mutant subunits; these effects were counteracted by the selective Kv7 opener retigabine and by gabapentin, a recently described Kv7 activator. Given these data, the patient started treatment with gabapentin, showing a rapid and sustained clinical and EEG improvement over the following months. Overall, these results suggest that gabapentin can be regarded as a precision therapy for DEEs due to KCNQ2 loss-of-function mutations.
Kv7.2 电压依赖性神经元钾 (K) 通道亚基编码的 KCNQ2 中的从头变异与发育性癫痫性脑病 (DEE) 有关。我们在此描述了由新型 KCNQ2 p.G310S 变异引起的早发性 DEE 患儿的临床和脑电图 (EEG) 特征。体外实验表明，该突变导致由包含突变亚基的通道产生的电流丧失功能效应；这些效应被选择性 Kv7 opener retigabine 和gabapentin（一种最近描述的 Kv7 激活剂）拮抗。鉴于这些数据，患者开始用gabapentin 治疗，在接下来的几个月中，临床和 EEG 迅速且持续改善。总的来说，这些结果表明，gabapentin 可以被视为由于 KCNQ2 功能丧失突变引起的 DEE 的精准治疗。
