Hippocampal sclerosis (HS) is one of the most prevalent pathological types of temporal lobe epilepsy (TLE), and it significantly affects patient prognoses. The methylation of DNA plays an important role in the development of epilepsy. However, few studies have focused on HS subtypes to determine DNA methylation profiles in TLE. This study aimed to determine the pathogenesis of TLE from an epigenetic perspective in patients with TLE-HS type I (TLE-HSTI) and TLE without HS (TLE-nHS) using whole-genome bisulfite sequencing (WGBS). We defined 1171 hypermethylated and 2537 hypomethylated regions and found 632 differentially methylated genes (DMG) in the promoter region that were primarily involved in the regulation of various aspects of epilepsy development. Twelve DMG overlapped with differentially expressed genes (DEG) in the promoter region, and RT-qPCR findings revealed significant overexpression of the SBNO2, CBX3, RASAL3, and TMBIM4 genes in TLE-HSTI. We present the first systematic analysis of methylation profiles of TLE-HSTI and TLE-nHS from an epigenetic perspective using WGBS. Overall, our preliminary data highlight the underlying mechanism of TLE-HSTI, providing a new perspective for guiding treatment of TLE.

海马硬化（HS）是颞叶癫痫（TLE）最普遍的病理类型之一，它显着影响患者的预后。DNA的甲基化在癫痫的发生发展中起重要作用。然而，很少有研究关注 HS 亚型来确定 TLE 中的 DNA 甲基化谱。本研究旨在使用全基因组亚硫酸氢盐测序 (WGBS) 从表观遗传学角度确定 TLE-HS I 型 (TLE-HSTI) 和无 HS 的 TLE (TLE-nHS) 患者的 TLE 发病机制。我们定义了 1171 个高甲基化区域和 2537 个低甲基化区域，并在启动子区域发现了 632 个差异甲基化基因 (DMG)，这些基因主要参与调节癫痫发展的各个方面。十二个DMG与启动子区域中的差异表达基因（DEG）重叠，TLE-HSTI 中的SBNO2、CBX3、RASAL3和TMBIM4基因。我们使用 WGBS 从表观遗传的角度首次系统分析了 TLE-HSTI 和 TLE-nHS 的甲基化谱。总体而言，我们的初步数据突出了 TLE-HSTI 的潜在机制，为指导 TLE 的治疗提供了新的视角。