Abstract
Insulin gene (INS) mutations are associated with a rare form of maturity-onset diabetes of the young (MODY). Here, we describe a proband with early-onset diabetes resulting from a heterozygous mutation in the promoter region of INS and summarize the clinical features of INS mutations caused by MODY (INS-MODY) reported in previous studies. The proband presented with proteinuria, mild hyperglycemia, and hypertension at the age of 39 years old; he was negative for the glutamic acid decarboxylase (GAD) antibody and had a family history of diabetes, including his father and aunt. The proband underwent whole exome sequencing, and the mutation in the proband and his father was verified by Sanger sequencing. A literature review was performed to examine all reported cases of INS-MODY to evaluate the clinical characteristics of the probands. A heterozygous INS mutation (c.-332C > G) was detected in the proband and his father, and their phenotypes had unique characteristics. Previous reports have described a total of 26 probands with 16 pathogenic mutations of the INS gene, with clinical features that exhibit great inter- and intrafamilial variability, and onset ages ranging from 2 years, 10 months to 62 years; 88% of patients were diagnosed before 40 years of age. Heterozygous mutations in the promoter region affecting the transcriptional activity of the INS gene may increase the risk of early-onset diabetes in adults, with patients presenting phenotypes that are very similar to type 2 diabetes, and genetic testing is needed to identify these individuals.
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All datasets are available from the corresponding authors upon reasonable request.
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Acknowledgements
We thank the study proband and his father for their contributions. We also thank all research staff for their collection of data.This study was supported by grants from National Key Research and Development Program of China (2016YFC1304901), Beijing Municipal Science and Technology Commission Funding (Z141100007414002 andD131100005313008).
Funding
This study was supported by grants from National Key Research and Development Program of China (2016YFC1304901), Beijing Municipal Science and Technology Commission Funding (Z141100007414002 and D131100005313008).
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The study protocol was approved by the Ethics Committee of Peking University People’s Hospital (China). Written informed consent was obtained from the proband and his father.
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Gong, S., Han, X. & Ji, L. A heterozygous mutation at promoter region of insulin gene (INS) accounts for early-onset diabetes: A case report and review of the literature. Int J Diabetes Dev Ctries 44, 145–149 (2024). https://doi.org/10.1007/s13410-023-01205-4
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DOI: https://doi.org/10.1007/s13410-023-01205-4