Dhindsa Ryan S, Goldstein David B
Institute for Genomic Medicine, Columbia University, Hammer Building, 701 West 168th Street, Box 149, New York, NY, 10032, USA,
Curr Neurol Neurosci Rep. 2015 Oct;15(10):70. doi: 10.1007/s11910-015-0587-4.
Epilepsy is a serious neurological disease with substantial genetic contribution. We have recently made major advances in understanding the genetics and etiology of the epilepsies. However, current antiepileptic drugs are ineffective in nearly one third of patients. Most of these drugs were developed without knowledge of the underlying causes of the epilepsy to be treated; thus, it seems reasonable to assume that further improvements require a deeper understanding of epilepsy pathophysiology. Although once the rate-limiting step, gene discovery is now occurring at an unprecedented rapid rate, especially in the epileptic encephalopathies. However, to place these genetic findings in a biological context and discover treatment options for patients, we must focus on developing an efficient framework for functional evaluation of the mutations that cause epilepsy. In this review, we discuss guidelines for gene discovery, emerging functional assays and models, and novel therapeutics to highlight the developing framework of precision medicine in the epilepsies.
癫痫是一种具有显著遗传因素的严重神经系统疾病。我们最近在理解癫痫的遗传学和病因学方面取得了重大进展。然而，目前的抗癫痫药物在近三分之一的患者中无效。这些药物大多是在对所治疗癫痫的潜在病因缺乏了解的情况下开发的；因此，有理由认为，进一步的改进需要更深入地了解癫痫的病理生理学。尽管基因发现曾经是限速步骤，但现在正以前所未有的速度进行，尤其是在癫痫性脑病中。然而，为了将这些遗传学发现置于生物学背景下并为患者发现治疗选择，我们必须专注于开发一个有效的框架，用于对导致癫痫的突变进行功能评估。在这篇综述中，我们讨论了基因发现的指导原则、新兴的功能检测和模型以及新型疗法，以突出癫痫精准医学的发展框架。
