{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:19:00Z","timestamp":1790144340119,"version":"4.0.1"},"reference-count":39,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United Kingdom Medical Research Council","award":["G1000467"],"award-info":[{"award-number":["G1000467"]}]},{"DOI":"10.13039\/501100014382","name":"Ipsen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid tumors, pituitary adenomas, and pancreatic neuroendocrine neoplasms (PNENs). MEN1 is caused by germline MEN1 mutations in\u2005&amp;gt;\u200575% of patients, and the remaining 25% of patients may have mutations in unidentified genes or represent phenocopies with mutations in genes such as cell cycle division 73 (CDC73), the calcium sensing receptor (CASR), and cyclin-dependent kinase inhibitor 1B (CDKN1B), which are associated with the hyperparathyroidism-jaw tumor syndrome, familial hypocalciuric hypercalcemia type 1, and MEN4, respectively. Here, we report a heterozygous c.1138C&amp;gt;T (p.Leu380Phe) CDC73 germline variant in a clinically diagnosed MEN1 patient, based on combined occurrence of primary hyperparathyroidism, acromegaly, and a PNEN. Characterization of the PNEN confirmed it was a neuroendocrine neoplasm as it immuno-stained positively for chromogranin and glucagon. The rare variant p.Leu380Phe occurred in a highly conserved residue, and further analysis using RNA-Scope indicated that it was associated with a significant reduction in CDC73 expression in the PNEN. Previously, CDC73 mutations have been reported to be associated with tumors of the parathyroids, kidneys, uterus, and exocrine pancreas. Thus, our report of a patient with PNEN and somatotrophinoma who had a CDC73 variant, provides further evidence that CDC73 variants may result in a MEN1 phenocopy.<\/jats:p>","DOI":"10.1210\/jendso\/bvaa142","type":"journal-article","created":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T08:04:40Z","timestamp":1601107480000},"source":"Crossref","is-referenced-by-count":13,"title":["Multiple Endocrine Neoplasia Type 1 (MEN1) Phenocopy Due to a Cell Cycle Division 73 (<i>CDC73<\/i>) Variant"],"prefix":"10.1210","volume":"4","author":[{"given":"Kate E","family":"Lines","sequence":"first","affiliation":[{"name":"Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa B","family":"Nachtigall","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital\/Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E","family":"Dichtel","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital\/Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Treena","family":"Cranston","sequence":"additional","affiliation":[{"name":"Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Boon","sequence":"additional","affiliation":[{"name":"Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital\/Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kreepa G","family":"Kooblall","sequence":"additional","affiliation":[{"name":"Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh V","family":"Thakker","sequence":"additional","affiliation":[{"name":"Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,9,26]]},"reference":[{"issue":"4","key":"2020120619234643300_CIT0001","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nrendo.2018.3","article-title":"Current and emerging therapies for PNETs in patients with or without MEN1","volume":"14","author":"Frost","year":"2018","journal-title":"Nat Rev Endocrinol."},{"issue":"6","key":"2020120619234643300_CIT0002","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1056\/NEJMc1406028","article-title":"Breast-cancer predisposition in multiple endocrine neoplasia type 1","volume":"371","author":"Dreijerink","year":"2014","journal-title":"N Engl J Med."},{"issue":"1","key":"2020120619234643300_CIT0003","doi-asserted-by":"crossref","first-page":"E1089","DOI":"10.1002\/humu.21170","article-title":"Diagnostic challenges due to phenocopies: lessons from multiple endocrine neoplasia type1 (MEN1)","volume":"31","author":"Turner","year":"2010","journal-title":"Hum Mutat."},{"issue":"2","key":"2020120619234643300_CIT0004","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000443167","article-title":"ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site","volume":"103","author":"Pavel","year":"2016","journal-title":"Neuroendocrinology."},{"issue":"9","key":"2020120619234643300_CIT0005","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1210\/jc.2012-1230","article-title":"Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)","volume":"97","author":"Thakker","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"key":"2020120619234643300_CIT0006","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3389\/fendo.2019.00339","article-title":"Multiple endocrine neoplasia type 1 (MEN1): an update and the significance of early genetic and clinical diagnosis","volume":"10","author":"Kamilaris","year":"2019","journal-title":"Front Endocrinol (Lausanne)."},{"issue":"1","key":"2020120619234643300_CIT0007","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12916-016-0708-1","article-title":"MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients","volume":"14","author":"de Laat","year":"2016","journal-title":"BMC Med."},{"issue":"1-2","key":"2020120619234643300_CIT0008","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cancergen.2015.12.002","article-title":"Multiple endocrine neoplasia type 1 (MEN1): an update of 208 new germline variants reported in the last nine years","volume":"209","author":"Concolino","year":"2016","journal-title":"Cancer Genet."},{"issue":"1","key":"2020120619234643300_CIT0009","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/humu.20605","article-title":"Multiple endocrine neoplasia type 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cells","volume":"124","author":"Chamberlain","year":"2014","journal-title":"J Clin Invest."}],"container-title":["Journal of the Endocrine 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