Focal cortical dysplasia (FCD) is a malformation of the cerebral cortex with poorly-defined epileptogenic zones (EZs), and poor surgical outcome in FCD is associated with inaccurate localization of the EZ. Hence, identifying novel epileptogenic markers to aid in the localization of EZ in patients with FCD is very much needed. High-throughput gene expression studies of FCD samples have the potential to uncover molecular changes underlying the epileptogenic process and identify novel markers for delineating the EZ. For this purpose, we, for the first time performed RNA sequencing of surgically resected paired tissue samples obtained from electrocorticographically graded high (MAX) and low spiking (MIN) regions of FCD type II patients and autopsy controls. We identified significant changes in the MAX samples of the FCD type II patients when compared to non-epileptic controls, but not in the case of MIN samples. We found significant enrichment for myelination, oligodendrocyte development and differentiation, neuronal and axon ensheathment, phospholipid metabolism, cell adhesion and cytoskeleton, semaphorins, and ion channels in the MAX region. Through the integration of both MAX vs non-epileptic control and MAX vs MIN RNA sequencing (RNA Seq) data, PLP1, PLLP, UGT8, KLK6, SOX10, MOG, MAG, MOBP, ANLN, ERMN, SPP1, CLDN11, TNC, GPR37, SLC12A2, ABCA2, ABCA8, ASPA, P2RX7, CERS2, MAP4K4, TF, CTGF, Semaphorins, Opalin, FGFs, CALB2, and TNC were identified as potential key regulators of multiple pathways related to FCD type II pathology. We have identified novel epileptogenic marker elements that may contribute to epileptogenicity in patients with FCD and could be possible markers for the localization of EZ.

中文翻译：

---

高和低尖峰区域的转录组分析揭示了局灶性皮质发育不良 II 型患者的新致癫痫机制

局灶性皮质发育不良 (FCD) 是一种大脑皮层畸形，具有不明确的致癫痫区 (EZ)，FCD 的手术结果不佳与 EZ 的定位不准确有关。因此，非常需要鉴定新的致癫痫标志物以帮助 FCD 患者中 EZ 的定位。FCD 样本的高通量基因表达研究有可能揭示致癫痫过程背后的分子变化，并确定用于描绘 EZ 的新标记。为此，我们首次对从 FCD II 型患者和尸检对照的皮质电分级高 (MAX) 和低尖峰 (MIN) 区域获得的手术切除的配对组织样本进行 RNA 测序。与非癫痫对照相比，我们发现 FCD II 型患者的 MAX 样本发生了显着变化，但 MIN 样本没有。我们发现 MAX 区域的髓鞘形成、少突胶质细胞发育和分化、神经元和轴突鞘、磷脂代谢、细胞粘附和细胞骨架、信号蛋白和离子通道显着富集。通过整合 MAX 与非癫痫控制和 MAX 与 MIN RNA 测序 (RNA Seq) 数据，PLP1、PLLP、UGT8、KLK6、SOX10、MOG、MAG、MOBP、ANLN、ERMN、SPP1、CLDN11、TNC、GPR37 、SLC12A2、ABCA2、ABCA8、ASPA、P2RX7、CERS2、MAP4K4、TF、CTGF、Semaphorins、Opalin、FGFs、CALB2 和 TNC 被确定为与 FCD II 型病理相关的多种途径的潜在关键调节因子。