Advancing epilepsy genetics in the genomic era.
Advancing epilepsy genetics in the genomic era.
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DOI：
10.1186/s13073-015-0214-7
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发表时间：
2015-08-25
期刊：
影响因子：
12.3
通讯作者：
Mefford HC
中科院分区：
文献类型：
--
作者：
Myers CT;Mefford HC
癫痫是一组以反复发作为特征的疾病，是最常见的神经系统疾病之一。癫痫的遗传基础从流行病学研究和在大家族中发现的罕见基因中是清楚的。癫痫疾病的三个主要类别是遗传性全身性癫痫、局灶性癫痫和脑病性癫痫，每个类别中有几种特定的疾病。基因组技术的进步，促进了常见和罕见变异的全基因组发现，导致我们对癫痫遗传学的理解迅速增加。拷贝数变异和全基因组关联研究有助于我们理解全身性癫痫的复杂遗传结构，而对局灶性癫痫和癫痫性脑病的遗传见解主要来自外显子组测序。越来越清楚的是，癫痫是遗传异质性的，新的基因发现已经超越了已知的离子通道的贡献，涉及染色质重塑，转录调节和调节哺乳动物雷帕霉素靶蛋白（mTOR）在癫痫的病因学领域。这些发现为新疗法铺平了道路，其中一些已经在研究中。在这篇综述中，我们讨论了基因组技术促进癫痫基因发现的快速步伐，并强调了几个新的基因和潜在的治疗方法。
Epilepsy is a group of disorders characterized by recurrent seizures, and is one of the most common neurological conditions. The genetic basis of epilepsy is clear from epidemiological studies and from rare gene discoveries in large families. The three major classes of epilepsy disorders are genetic generalized, focal and encephalopathic epilepsies, with several specific disorders within each class. Advances in genomic technologies that facilitate genome-wide discovery of both common and rare variants have led to a rapid increase in our understanding of epilepsy genetics. Copy number variant and genome-wide association studies have contributed to our understanding of the complex genetic architecture of generalized epilepsy, while genetic insights into the focal epilepsies and epileptic encephalopathies have come primarily from exome sequencing. It is increasingly clear that epilepsy is genetically heterogeneous, and novel gene discoveries have moved the field beyond the known contribution of ion channels to implicate chromatin remodeling, transcriptional regulation and regulation of the mammalian target of rapamycin (mTOR) protein in the etiology of epilepsy. Such discoveries pave the way for new therapeutics, some of which are already being studied. In this review, we discuss the rapid pace of gene discovery in epilepsy, as facilitated by genomic technologies, and highlight several novel genes and potential therapies.