Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2024; 15(2): 275-286
Published online Feb 15, 2024. doi: 10.4239/wjd.v15.i2.275
Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients
Ping Shi, Yang Tian, Feng Xu, Lu-Na Liu, Wan-Hong Wu, Ying-Zhou Shi, An-Qi Dai, Hang-Yu Fang, Kun-Xia Li, Chao Xu
Ping Shi, Yang Tian, Feng Xu, Lu-Na Liu, Wan-Hong Wu, Ying-Zhou Shi, An-Qi Dai, Hang-Yu Fang, Chao Xu, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Kun-Xia Li, Department of Pediatric, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai 264099, Shandong Province, China
Co-corresponding authors: Kun-Xia Li and Chao Xu.
Author contributions: Li KX and Xu C are the co-corresponding authors of this manuscript; Xu C acted as a guarantor for the research design and manuscript revision; Li KX designed the theme of the article; Shi P carried out the experiments and wrote the manuscript; Tian Y contributed to the experiment implementation and data collection; Xu F edited and reviewed the content of the manuscript; Liu LN and Wu WH contributed to the experiment implementation and data analysis; Shi YZ, Dai AQ, and Fang HY performed bioinformation analysis and graph drawing; and all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation, No. 81974124; and Taishan Scholar Project, No. tsqn20161071.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Shandong Provincial Hospital.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chao Xu, MD, Doctor, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Weiqi Road, Jinan 250021, Shandong Province, China. doctorxuchao@163.com
Received: October 2, 2023
Peer-review started: October 2, 2023
First decision: November 9, 2023
Revised: November 22, 2023
Accepted: January 9, 2024
Article in press: January 9, 2024
Published online: February 15, 2024
Core Tip

Core Tip: We identified five new mutations in the adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) gene, a critical regulator of insulin signaling and glucose metabolism, in maturity-onset diabetes of the young type 14 patients. We conducted bioinformatics and functional experiments and showed that two mutations were pathogenic, resulting in reduced expression of the APPL1 protein and mRNA. All mutations were in the phosphotyrosine-binding domain of APPL1, which is important for its insulin-sensitizing effect. This study gave new insights into the pathogenicity of APPL1 mutations in diabetes and revealed potential targets for improved diagnosis and treatment strategies.