Ahmed Elsadig Mohamed, Elangeeb Mohamed E, Adam Khalid Mohamed, Abuagla Hytham Ahmed, MohamedAhmed Abubakr Ali Elamin, Ali Elshazali Widaa, Eltieb Elmoiz Idris, Edris Ali M, Ali Osman Hiba Mahgoub, Idris Ebtehal Saleh, Khalil Khalil A A
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, P.O. Box 551, Bisha 61922, Saudi Arabia.
J Pers Med. 2024 Apr 17;14(4):425. doi: 10.3390/jpm14040425.
gene mutations affect the structure of insulin and are considered a leading cause of neonatal diabetes and permanent neonatal diabetes mellitus PNDM. These mutations can affect the production and secretion of insulin, resulting in inadequate insulin levels and subsequent hyperglycemia. Early discovery or prediction of PNDM can aid in better management and treatment. The current study identified potential deleterious non-synonymous single nucleotide polymorphisms nsSNPs in the gene. The analysis of the nsSNPs in the gene was conducted using bioinformatics tools by implementing computational algorithms including SIFT, PolyPhen2, SNAP2, SNPs & GO, PhD-SNP, MutPred2, I-Mutant, MuPro, and HOPE tools to investigate the prediction of the potential association between nsSNPs in the gene and PNDM. Three mutations, C96Y, P52R, and C96R, were shown to potentially reduce the stability and function of the protein. These mutants were subjected to MDSs for structural analysis. Results suggested that these three potential pathogenic mutations may affect the stability and functionality of the insulin protein encoded by the gene. Therefore, these changes may influence the development of PNDM. Further researches are required to fully understand the various effects of mutations in the gene on insulin synthesis and function. These data can aid in genetic testing for PNDM to evaluate its risk and create treatment and prevention strategies in personalized medicine.
基因突变会影响胰岛素的结构，被认为是新生儿糖尿病和永久性新生儿糖尿病（PNDM）的主要病因。这些突变会影响胰岛素的产生和分泌，导致胰岛素水平不足，进而引发高血糖。早期发现或预测PNDM有助于更好地进行管理和治疗。当前的研究在该基因中鉴定出了潜在有害的非同义单核苷酸多态性（nsSNPs）。通过使用生物信息学工具，实施包括SIFT、PolyPhen2、SNAP2、SNPs & GO、PhD-SNP、MutPred2、I-Mutant、MuPro和HOPE工具在内的计算算法，对该基因中的nsSNPs进行分析，以研究该基因中的nsSNPs与PNDM之间潜在关联的预测。结果显示，三种突变C96Y、P52R和C96R可能会降低该蛋白的稳定性和功能。对这些突变体进行了分子动力学模拟（MDSs）以进行结构分析。结果表明，这三种潜在的致病突变可能会影响该基因编码的胰岛素蛋白的稳定性和功能。因此，这些变化可能会影响PNDM的发展。需要进一步的研究来全面了解该基因中的突变对胰岛素合成和功能的各种影响。这些数据有助于进行PNDM的基因检测，以评估其风险，并在个性化医疗中制定治疗和预防策略。
