ALG13 (asparagine-linked glycosylation 13) plays crucial roles in the process of N-linked glycosylation. Mutations of the ALG13 gene underlie congenital disorders of glycosylation type I (CDG-I), a rare human genetic disorder with defective glycosylation. Epilepsy is commonly observed in congenital disorders of glycosylation type I (CDG-I). In our study, we found that about 20% of adult ALG13KO knockout mice display spontaneous seizures, which were identified in a simultaneous video and intracranial EEG recording. However, the mechanisms of ALG13 by which deficiency leads to epilepsy are unknown. Whole-cell patch-clamp recordings demonstrated that ALG13KO mice show a marked decrease in gamma-aminobutyric acid A receptor (GABA_AR)-mediated inhibitory synaptic transmission. Furthermore, treatment with low-dose diazepam (a positive allosteric modulator of GABA_A receptors), which enhances GABA_AR function, also markedly ameliorates severity of epileptic seizures in ALG13KO mice. Moreover, ALG13 may influenced the expression of GABA_ARα2 membrane and total protein by changing transcription level of GABA_ARα2. Furthermore, protein interactions between ALG13 and GABA_ARα2 were observed in the cortex of wild-type mice. Overall, these results reveal that ALG13 may be involved in the occurrence of epilepsy through the regulation of GABA_AR function, and may provide new insight into epilepsy prevention and treatment.

ALG13（天冬酰胺连接糖基化 13）在 N 连接糖基化过程中发挥着至关重要的作用。ALG13 基因突变是 I 型先天性糖基化疾病 (CDG-I) 的基础，这是一种罕见的糖基化缺陷人类遗传性疾病。癫痫常见于 I 型糖基化先天性疾病 (CDG-I)。在我们的研究中，我们发现约 20% 的成年 ALG13KO 敲除小鼠表现出自发性癫痫发作，这是在同步视频和颅内脑电图记录中发现的。然而，ALG13 缺陷导致癫痫的机制尚不清楚。全细胞膜片钳记录表明，ALG13KO 小鼠的 γ-氨基丁酸 A 受体 (GABA _A R) 介导的抑制性突触传递显着减少。此外，使用低剂量地西泮（GABA _A受体的正变构调节剂）治疗可增强 GABA _A R 功能，也可显着改善 ALG13KO 小鼠癫痫发作的严重程度。_{此外，ALG13可能通过改变GABA A Rα2的转录水平来影响GABA A} Rα2膜和总蛋白的表达。此外，在野生型小鼠的皮质中观察到ALG13 和 GABA _{A Rα2 之间的蛋白质相互作用。}总的来说，这些结果揭示了ALG13可能通过调节GABA _A R功能参与癫痫的发生，并可能为癫痫的预防和治疗提供新的见解。