Insights into INS Gene Variation from Seven Years of Monogenic Diabetes Testing—Novel Genetic Variants and Their Clinical Implications
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Le résumé fourni par la source
Monogenic diabetes (MD) is a rare and heterogeneous group of disorders caused by genetic variants in genes involved in glucose metabolism. Among many MD genes, the insulin gene (INS) deserves special attention, as its variants are responsible for both permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM), as well as a form of MODY (maturity-onset diabetes of the young)—INS-MODY. The aim of the study was to perform a clinical and molecular analysis of patients focused on the evaluation of INS gene variants identified during molecular testing in patients referred with suspected MD, and to assess the prediction of their impact on protein structure using in silico methods. Between 2017 and 2024, 1043 unrelated probands were tested using targeted next-generation sequencing (tNGS) panels. Three pathogenic or likely pathogenic variants in the INS gene were identified in three unrelated families, indicating that this gene accounts for 0.38% of MD cases. This allowed for the diagnosis of PNDM in two patients with diabetes diagnosed within the first four months of life and INS-MODY in a patient with diabetes since the age of 16. Moreover, in the patient with PNDM and the INS:c.T104C variant, additional disorders were identified in the form of intrauterine growth restriction (IUGR) and neurological disorders. Importantly, two of the identified genetic variants, c.C103G and c.G3C, have not previously been described in the literature. Furthermore, in silico analysis of the variants at the protein level, i.e., investigation of mutations at the 35th residue, indicated that symptom severity correlates with the extent of structural changes in insulin. The results obtained broaden the spectrum of causative variants of the INS gene, but also emphasize the clinical significance of these variants in patients with various forms of diabetes, pointing to the key role of comprehensive genetic testing in enabling accurate diagnosis and targeted treatment of patients.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Insights into INS Gene Variation from Seven Years of Monogenic Diabetes Testing—Novel Genetic Variants and Their Clinical Implications
- Date Crossref
- 13/01/2026
- Éditeur
- MDPI AG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Medical University of Lodz Department of Clinical Genetics pays non établi dans la noticeUniversité ou école supérieure
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Medical University of Białystok pays non établi dans la noticeUniversité ou école supérieure
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Wroclaw Medical University pays non établi dans la noticeUniversité ou école supérieure
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Medical University of Warsaw Department of Diabetology and Internal Medicine pays non établi dans la noticeUniversité ou école supérieure
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Gdańsk Medical University pays non établi dans la noticeUniversité ou école supérieure
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University of Debrecen pays non établi dans la noticeUniversité ou école supérieure
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Medical University of Bialystok Metabolomics and Proteomics Laboratory pays non établi dans la noticeUniversité ou école supérieure
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University Clinical Hospital Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Medical University of Gdansk Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Medicine Department of Biochemistry and Molecular Biology pays non établi dans la noticeUniversité ou école supérieure
Department of Clinical Genetics — Medical University of Lodz, Medical University of Białystok et Wroclaw Medical University, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.