{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:48:53Z","timestamp":1788349733663,"version":"build-2803163510"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":39,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIDDK, NIH","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,24]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Among patients with multiple endocrine neoplasia type 1 (MEN1), 80% develop duodenopancreatic neuroendocrine tumors (dpNETs), of whom 15%\u201325% die of metastasis. There is a need to identify biomarkers to predict aggressive disease.\n                      <jats:italic>MEN1<\/jats:italic>\n                      genotype affords an attractive possibility as a biomarker, as it remains constant during life. Currently, patients are clinically diagnosed with MEN1 by the presence of \u22652 primary endocrine tumors (pituitary, parathyroid, and pancreas) or \u22651 primary endocrine tumor with a positive family history. From 10% to 30% of patients diagnosed clinically with MEN1 have no pathogenic germline\n                      <jats:italic>MEN1<\/jats:italic>\n                      variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This was a retrospective study of 162 index patients or probands with genotype-positive and 47 with genotype-negative MEN1 enrolled from 1977 to 2022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Compared with patients with genotype-negative disease, patients with genotype-positive disease were younger at diagnosis and had an increased frequency of recurrent parathyroid tumors, dpNETs, and angiofibromas or collagenomas. We propose a weighted scoring system to diagnose genotype-positive MEN1 based on clinical characteristics. No evidence of MEN1 mosaicism was seen in 30 tumors from 17 patients with genotype-negative MEN1. Patients with germline MEN1 variants in exons 2 and 3 had a reduced risk of distant metastases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The clinical course of genotype-negative MEN1 is distinct from genotype-positive disease, raising uncertainty about the benefits of lifetime surveillance in patients with genotype-negative disease. MEN1 mosaicism is rare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT04969926<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Intramural Research Program of National Institute of Diabetes and Digestive and Kidney Diseases, NIH (ZIA DK043006-46)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.176993","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T12:00:57Z","timestamp":1739448057000},"source":"Crossref","is-referenced-by-count":8,"title":["Genotype-phenotype correlation in multiple endocrine neoplasia type 1"],"prefix":"10.1172","volume":"10","author":[{"given":"Charlita C.","family":"Worthy","sequence":"first","affiliation":[{"name":"Metabolic Diseases 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