非综合征型唇腭裂（NSCLP）是基因、环境等共同作用的结果，其发病机理尚不明确。RESP18是促肾上腺皮质激素分泌途径中的糖皮质激素反应蛋白，与糖基化修饰密切相关并参与胚胎颅面部发育。糖基化修饰使蛋白结构更复杂，功能更完善，进而影响细胞生长迁移及器官发育。前期我们发现：NSCLP家系中RESP18基因位点rs2385405和rs2385404突变；下调RESP18表达抑制OGT介导的AMPK蛋白糖基化修饰，阻滞细胞周期，从而影响人腭胚间充质细胞的生长迁移；地塞米松可抑制RESP18表达及蛋白质糖基化，并诱导胎鼠腭裂发生。因此，我们推测RESP18调控OGT介导的糖基化修饰，调节细胞周期及自噬，控制细胞生长迁移及腭器官发育，最终影响唇腭裂发生。本项目拟通过临床样本、细胞实验及动物模型，探讨RESP18与OGT调控蛋白糖基化修饰在唇腭裂发生中的作用机制及临床意义，为NSCLP防治提供新的思路。

Non-syndromic cleft lip and palate （NSCLP） is the result of gene and environment, and its pathogenesis needs to be further elucidated. Resp18 is a glucocorticoid responsive protein in the adrenocorticotropic hormone secretion pathway, which is closely related to glycosylation and participates in the embryonic craniofacial development. Glycosylation makes protein more complex structure and more perfect function, and then affects cell growth, migration and organ development. In our previous experiments, we found that rs2385405 and rs2385404 mutations of Resp18 gene were discovered in NSCLP family; Down-regulating the expression of Resp18 can inhibit the glycosylation of AMPK protein mediated by OGT and block cell cycle, thus affect the growth and migration of human embryonic palatal mesenchymal cells; Dexamethasone can inhibit the expression of Resp18 and protein glycosylation, and induce cleft palate in fetal rats. Therefore, we speculate that RESP18 regulates OGT mediated glycosylation, cell cycle and autophagy, cell growth and migration, and development of palatal organs, and ultimately affects the development of cleft lip and palate. This project aims to explore the mechanism and clinical significance of RESP18 and OGT mediated proteins glycosylation in the development of cleft lip and palate through clinical samples, cell experiments and animal models, so as to provide new ideas for the prevention and treatment of NSCLP.