Genetics of the epilepsies: where are we and where are we going?
Genetics of the epilepsies: where are we and where are we going?
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DOI：
10.1097/wco.0b013e32835ee6ff
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发表时间：
2013-04
影响因子：
4.8
通讯作者：
Lowenstein DH
中科院分区：
文献类型：
--
作者：
Helbig I;Lowenstein DH
本文综述了癫痫遗传学领域的最新进展，重点介绍了单基因癫痫的基因发现、复杂遗传癫痫的危险基因鉴定以及癫痫药物基因组学领域的最新发现。在过去的12个月里，大量平行测序技术的使用使得发现了几个单基因癫痫的基因。最重要的是，PRRT2被确定为寻找已久的良性家族性婴儿癫痫（BFIS）基因。KCNT1突变在两种看似无关的单基因癫痫中被发现，包括婴儿期恶性迁移性部分癫痫（MMPSI）和严重常染色体显性夜间额叶癫痫（ADNFLE）。一项针对特发性广泛性癫痫（IGE）的全基因组关联研究揭示了人类癫痫发作疾病的首批常见风险变异，包括VRK2、PNPO和SCN1A的变异。此外，一项具有里程碑意义的研究提供了证据，证明筛选HLAB*1502变异可以预防卡马西平在台湾人群中引起的副作用。此外，HLA-A*3101变异被确定为欧洲人卡马西平副作用的危险因素。新技术和前所未有的国际合作水平导致了单基因和复杂遗传性癫痫的新基因以及抗癫痫药物副作用的危险因素。本文综述了过去一年中最相关的研究，并强调了该领域未来的发展方向。
We aim to review the most recent advances in the field of epilepsy genetics with particular focus on the progress in gene discovery in monogenic epilepsies, identification of risk genes in complex genetic epilepsies and recent findings in the field of epilepsy pharmacogenomics. During the last 12 months, the use of massive parallel sequencing technologies has allowed for the discovery of several genes for monogenic epilepsies. Most importantly, PRRT2 was identified as the long-sought gene for Benign Familial Infantile Seizures (BFIS). Mutations in KCNT1 were found in two seemingly unrelated monogenic epilepsies including Malignant Migrating Partial Seizures of Infancy (MMPSI) and severe Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE). A genome-wide association study in Idiopathic Generalized Epilepsy (IGE) revealed the first common risk variants for human seizure disorders including variants in VRK2, PNPO and SCN1A. Furthermore, a landmark study provided evidence that screening for the HLAB*1502 variant may prevent carbamazepine-induced side effects in the Taiwanese population. Also, HLA-A*3101 variants were identified as a risk factor for carbamazepine side effects in Europeans. Novel technologies and an unprecedented level of international collaboration has resulted in novel genes for monogenic and complex genetic epilepsies as well as risk factors for side effects of antiepileptic drugs. This review provides an overview of the most relevant studies in the last year and highlights the future direction of the field.