Genetic and epigenetic mechanisms of epilepsy: a review.
Genetic and epigenetic mechanisms of epilepsy: a review.
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DOI：
10.2147/ndt.s142032
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发表时间：
2017
影响因子：
3.2
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Chen T;Giri M;Xia Z;Subedi YN;Li Y
癫痫是一种常见的发作性神经系统疾病或状况，其特征是反复发作的癫痫发作，遗传学似乎在其病因学中起着关键作用。早期的连锁研究已经定位了多个位点，这些位点可能含有癫痫易感基因，突变分析已经检测到特发性癫痫患者中涉及离子通道和非离子通道基因的一些突变。癫痫的全基因组研究发现了2q24.2-q24.3，7q11.22，15q11.2-q13.3和16p13.11-p13.2的拷贝数变异，其中一些破坏了多个基因，如NRXN 1，AUTS 2，NLGN 1，CNTNAP 2，GRIN 2A，PRRT 2，NIPA 2和BMP 5，涉及神经发育障碍，包括智力残疾和自闭症。不幸的是，只有少数常见的遗传变异与癫痫有关。最近的外显子组测序研究发现了一些基因突变，其中大多数位于非离子通道基因如LGI 1，PRRT 2，EFHC 1，PRICKLE，RBFOX 1和DEPDC 5以及罕见家族性癫痫的先证者中，其中一些基因与神经发育有关。由于表观遗传学在胚胎发生和早期脑发育到组织特异性基因表达的神经元功能中起作用，表观遗传调控可能有助于神经发育的遗传机制，通过该机制，基因和环境相互作用影响癫痫的发展。本文综述了用于识别癫痫的分析工具，并对最近的连锁和关联研究结果进行了总结，指出了几条染色体上新基因的存在，以进一步了解癫痫的生物学。
Epilepsy is a common episodic neurological disorder or condition characterized by recurrent epileptic seizures, and genetics seems to play a key role in its etiology. Early linkage studies have localized multiple loci that may harbor susceptibility genes to epilepsy, and mutational analyses have detected a number of mutations involved in both ion channel and nonion channel genes in patients with idiopathic epilepsy. Genome-wide studies of epilepsy have found copy number variants at 2q24.2-q24.3, 7q11.22, 15q11.2-q13.3, and 16p13.11-p13.2, some of which disrupt multiple genes, such as NRXN1, AUTS2, NLGN1, CNTNAP2, GRIN2A, PRRT2, NIPA2, and BMP5, implicated for neurodevelopmental disorders, including intellectual disability and autism. Unfortunately, only a few common genetic variants have been associated with epilepsy. Recent exome-sequencing studies have found some genetic mutations, most of which are located in nonion channel genes such as the LGI1, PRRT2, EFHC1, PRICKLE, RBFOX1, and DEPDC5 and in probands with rare forms of familial epilepsy, and some of these genes are involved with the neurodevelopment. Since epigenetics plays a role in neuronal function from embryogenesis and early brain development to tissue-specific gene expression, epigenetic regulation may contribute to the genetic mechanism of neurodevelopment through which a gene and the environment interacting with each other affect the development of epilepsy. This review focused on the analytic tools used to identify epilepsy and then provided a summary of recent linkage and association findings, indicating the existence of novel genes on several chromosomes for further understanding of the biology of epilepsy.