{
  "abstract": "Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited syndrome characterized by primary hyperparathyroidism (PHPT), duodenopancreatic neuroendocrine tumors (DP-NET), pituitary NET (Pit-NET) and other endocrine neoplasms. Reliable genotype–phenotype correlations remain limited, and the clinical relevance of MEN1 exon 2 variants is still uncertain. Methods and aim: This monocentric retrospective cohort included genetically confirmed MEN1 patients followed at the University of Naples Federico II from January 1992 to April 2025. Eligible patients carried a pathogenic MEN-1 variant involving a single exon and had at least 36 months of follow-up. Clinical, biochemical, radiological, histopathological, genetic, and treatment data were reviewed to compare patients carrying exon 2 variants (Ex2) with those carrying variants in other exons (OtherEx) in order to evaluate mean age at diagnosis (TD) and aggressiveness of MEN-1 manifestations in these two groups. Results: Sixty patients were included: 21 Ex2 and 39 OtherEx. Follow-up was comparable between groups (133 +/− 47.7 vs. 128 +/− 50.0 months). PHPT, Pit-NET, and DP-NET had similar prevalence. DP-NET metastases were more frequent in Ex2 than OtherEx patients (4/21, 19.0% vs. 1/39, 2.6%; OR 8.94, 95% CI 0.93–86.09; p = 0.0465). When the analysis was restricted to patients who developed DP-NET, metastatic disease occurred in 4/16 Ex2 patients (25.0%) and 1/30 OtherEx patients (3.3%; OR 9.67, 95% CI 0.98–95.68; p = 0.0430). Mean DP-NET progression-free survival was numerically shorter in Ex2 patients, without statistical significance (99.6 vs. 121.6 months; p = 0.27), and DP-NET-related deaths occurred only in the Ex2 group. Additional exploratory signals included male-specific adrenal adenomas among Ex2 patients and exon 7-related bone impairment. Conclusions: This long-term MEN1 cohort suggests that exon 2 variants may identify patients with similar DP-NET prevalence but greater metastatic propensity. Because of the number of metastatic events, these findings require validation in larger multicenter cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Elio Benevento",
      "orcid": "0000-0002-4489-3651"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessia Liccardi"
    },
    {
      "affs": [
        0
      ],
      "name": "Roberto Minotta",
      "orcid": "0000-0002-8823-0702"
    },
    {
      "affs": [
        0
      ],
      "name": "Gianfranco Di Iasi",
      "orcid": "0009-0001-9737-9912"
    },
    {
      "affs": [
        0
      ],
      "name": "Massimo Di Nola",
      "orcid": "0009-0003-3508-980X"
    },
    {
      "affs": [
        0
      ],
      "name": "Michele Coletta",
      "orcid": "0009-0008-0656-257X"
    },
    {
      "affs": [
        0
      ],
      "name": "Annamaria Colao",
      "orcid": "0000-0001-6986-266X"
    },
    {
      "affs": [
        0
      ],
      "name": "Roberta Modica",
      "orcid": "0000-0002-3768-5803"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9h7mv6q26cewy.bib",
  "cited_by": 0,
  "doi": "10.3390/metabo16110859",
  "fulltext_url": null,
  "id": "9h7mv6q26cewy",
  "issns": [
    "2218-1989"
  ],
  "landing_url": "https://www.mdpi.com/2218-1989/16/11/859",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/9h7mv6q26cewy.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T00:21:13Z",
      "native_id": "10.3390/metabo16110859",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-1989/16/11/859"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:2218-1989",
      "subfield": "proteomics-metabolomics"
    }
  ],
  "title": "Clinical and Pathological Features of Patients with Multiple Endocrine Neoplasia Type 1: A Long-Term Comparative Analysis Between Exon 2 and Other Mutations in the MEN1 Gene",
  "title_text": "Clinical and Pathological Features of Patients with Multiple Endocrine Neoplasia Type 1: A Long-Term Comparative Analysis Between Exon 2 and Other Mutations in the MEN1 Gene",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T00:22:29Z",
  "url": "https://research.draconitic.com/paper/9h7mv6q26cewy",
  "venue": "Metabolites",
  "versions": []
}