The Necessity of POMC and MC3R Analysis in the First-Level Diagnosis of Monogenic Obesity: The Experience of Two Italian Centers
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Le résumé fourni par la source
Background/Objectives: Obesity is a global health emergency with a complex etiology, in which monogenic forms, although rare, are significantly underdiagnosed. In our clinical setting, first-tier genetic screening panels targeting LEP, LEPR, BDNF, FTO, and MC4R often fail to identify a causative variant, leaving a significant diagnostic gap. This study aimed to assess the prevalence of variants in other critical genes of the melanocortin pathway to improve diagnostic yield. Methods: We analyzed 88 patients with non-syndromic obesity (Body Mass Index, BMI > 30 kg/m2), who were first screened for our standard obesity-related genes. In those testing negative, we expanded the analysis to include the MC3R and POMC genes. In silico bioinformatic tools were used to predict the functional consequences of identified variants on protein structure and splicing. Results: We found several variants in POMC, specifically within the regions coding for alpha-, beta-, and gamma-MSH peptides. A bioinformatic analysis suggests that these variants disrupt the melanocortin signaling pathway, likely contributing to an intermediate susceptibility phenotype in our adult cohort. Additionally, a clinical follow-up of a patient carrying the rare BDNF p.Thr2Ile variant revealed a suboptimal response to high-dose tirzepatide treatment (9% weight loss over 72 weeks), notably inferior to the average response observed in clinical trials. Conclusions: Our findings demonstrate that expanding first-level routine testing to include POMC and MC3R is essential to maximize diagnostic yield and improve clinical management.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The Necessity of POMC and MC3R Analysis in the First-Level Diagnosis of Monogenic Obesity: The Experience of Two Italian Centers
- Date Crossref
- 31/03/2026
- 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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University of Siena Department of Medical pays non établi dans la noticeUniversité ou école supérieure
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Fondazione Istituto G. Giglio di Cefalù pays non établi dans la noticeInstitution
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Saint Camillus International University of Health and Medical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Ospedale San Donato pays non établi dans la noticeÉtablissement de santé
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Simple Operating Unit of Endocrine Surgery pays non établi dans la noticeInstitution
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Faculty of Medicine pays non établi dans la noticeUniversité ou école supérieure
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Operating Unit of Internal Medicine pays non établi dans la noticeInstitution
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Simple Operating Unit of General Surgery pays non établi dans la noticeInstitution
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Simple Operating Departmental Unit of Endocrinology pays non établi dans la noticeInstitution
Department of Medical — University of Siena, Fondazione Istituto G. Giglio di Cefalù et Saint Camillus International University of Health and Medical Sciences, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.