Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, 72076, Germany.
Division of Neurology and Developmental Neuroscience, Epilepsy and Neurophysiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
Ann Clin Transl Neurol. 2023 Apr;10(4):656-663. doi: 10.1002/acn3.51742. Epub 2023 Feb 15.
Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage-gated K channel subunit K 1.1. So far, loss-of-function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain-of-function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4-aminopyridine. Clinical use of 4-aminopyridine was associated with reduced seizure burden, enabled simplification of co-medication and prevented rehospitalization.
孟德尔遗传性癫痫的精准医疗正在迅速发展。我们描述了一例早发性婴儿严重药物难治性多灶性癫痫。外显子组测序显示 KCNA1 基因（编码电压门控钾通道亚基 K1.1）的新生变异 p.(Leu296Phe)。到目前为止，KCNA1 的功能丧失变异与发作性共济失调 1 型或癫痫有关。在卵母细胞中对突变亚基的功能研究显示，电压依赖性的超极化移位导致功能获得。Leu296Phe 通道对 4-氨基吡啶敏感。临床使用 4-氨基吡啶与减少癫痫发作负担有关，使联合用药简化，并防止再住院。
