Table_1_Overdosage of HNF1B Gene Associated With Annular Pancreas Detected in Neonate Patients With 17q12 Duplication.docx

The annular pancreas (AP) is a congenital anomaly of the pancreas that can cause acute abdominal pain and vomiting after birth. However, the genetic cause of AP is still unknown, and no study has reported AP in patients with 17q12 duplication. This study retrospectively analyzed the next-generation sequencing (NGS) data of individuals from January 2016 to June 2020 for 17q12 duplication. To identify the function of the key gene of HNF1B in the 17q12 duplication region, human HNF1B mRNA was microinjected into LiPan zebrafish transgenic embryos. A total of 19 cases of 17q12 duplication were confirmed. AP was diagnosed during exploratory laparotomy in four patients (21.1%). The other common features of 17q12 duplication included intellectual disability (50%), gross motor delay (50%), and seizures/epilepsy (31.58%). The ratio of the abnormal pancreas in zebrafish was significantly higher in the HNF1B overexpression models. In conclusion, we first reported AP in patients with duplication of the 17q12 region, resulting in the phenotype of 17q12 duplication syndrome. Furthermore, our zebrafish studies verified the role of the HNF1B gene in pancreatic development.

环形胰腺（annular pancreas, AP）是一种胰腺先天性发育畸形，可在新生儿出生后引发急性腹痛与呕吐症状。目前，环形胰腺的遗传学致病机制尚未阐明，且尚无研究报道17q12重复变异患者并发环形胰腺的病例。本研究对2016年1月至2020年6月期间的受试者下一代测序（next-generation sequencing, NGS）数据开展回顾性分析，以筛查17q12重复变异。为明确17q12重复区域内关键基因HNF1B的生物学功能，我们将人源HNF1B mRNA显微注射至LiPan转基因斑马鱼胚胎中。本研究共确诊19例17q12重复变异受试者，其中4例（21.1%）患者经剖腹探查术确诊为环形胰腺。17q12重复综合征的其他常见临床表型包括智力障碍（50%）、大运动发育迟缓（50%）以及癫痫发作/癫痫（31.58%）。功能实验结果显示，HNF1B过表达的斑马鱼模型中，胰腺异常发生率显著升高。综上，本研究首次报道17q12区域重复患者并发环形胰腺，该表型参与构成17q12重复综合征的临床表型谱。此外，本研究通过斑马鱼动物模型验证了HNF1B基因在胰腺发育过程中的关键作用。