Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Department of Nursing, Meiho University, Pingtung, Taiwan.
Clin Genet. 2017 Oct;92(4):397-404. doi: 10.1111/cge.12992. Epub 2017 Mar 30.
Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized.
We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing.
We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene.
Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.
卷曲螺旋结构域蛋白 5（DEPDC5）基因突变已成为各种家族性局灶性癫痫综合征的重要病因。然而，DEPDC5 突变在散发性局灶性癫痫患者中的意义尚未明确。
我们使用全外显子组测序研究了一个具有可变病灶的家族性局灶性癫痫家系。随后，我们对 293 例局灶性癫痫患者进行了研究，使用靶向重测序对 DEPDC5 的所有外显子进行了测序。
我们报道了一个台湾家族的新剪接位点突变，该突变影响 mRNA 剪接并激活下游哺乳动物雷帕霉素靶蛋白（mTOR）通路。在局灶性癫痫患者中，大多数（220/293）患者为无皮质发育畸形的散发性局灶性癫痫。其中 2 例（0.9%）患者 DEPDC5 基因存在可能致病性突变。
我们的研究结果表明，DEPDC5 不仅是家族性局灶性癫痫最常见的基因，也可能是散发性局灶性癫痫的重要基因。由于局灶性癫痫占所有癫痫的 60%以上，因此 mTORC1 抑制剂对 DEPDC5 基因突变引起的局灶性癫痫患者的疗效将是一个重要的未来研究方向。
