{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:12Z","timestamp":1784557032323,"version":"3.55.0"},"reference-count":9,"publisher":"Bioscientifica","issue":"3","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"\n Summary<\/jats:title>\n \n Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by germline-activating pathogenic variants in the\n RET<\/jats:italic>\n proto-oncogene. MEN2A is the most common subtype, with a risk for medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT), whereas MEN2B is less common and associated with MTC and PHEO along with mucosal neuromas. Little is known about the specific\n RET<\/jats:italic>\n germline heterozygous variant K666N. This variant has been described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. There is one case of MTC and bilateral PHEO. The\n RET<\/jats:italic>\n K666N variant is not stratified yet by the American Thyroid Association, and data are limited on pathogenicity; therefore, appropriate screening and treatment of asymptomatic\n RET<\/jats:italic>\n K666N carriers are unclear. Here, we report a family with a heterozygous germline\n RET<\/jats:italic>\n K666N variant. The proband was identified when she experienced cardiogenic shock and multi-organ failure after an elective hysterectomy and subsequently was found to have PHEO, with genetic testing revealing the\n RET<\/jats:italic>\n K666N germline variant. Patient consent was obtained through IRB protocol COMIRB #15-0516.\n <\/jats:p>\n <\/jats:sec>\n \n Learning Points<\/jats:title>\n \n \n \n The specific\n RET<\/jats:italic>\n germline heterozygous variant K666N is rare and described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. Our proband is much younger and has PHEO, MTC, and PHPT.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The\n RET<\/jats:italic>\n K666N germline variant appears to be a low penetrance variant for MEN2.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-24-0009","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T07:55:37Z","timestamp":1725436537000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":1,"title":["MEN2 phenotype in a family with germline heterozygous rare RET K666N variant"],"prefix":"10.1530","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6124-1305","authenticated-orcid":true,"given":"A","family":"La Greca","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Dawes","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Albuja-Cruz","sequence":"additional","affiliation":[{"name":"Division of GI, Trauma and Endocrine Surgery, Department of Surgery, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Raeburn","sequence":"additional","affiliation":[{"name":"Division of GI, Trauma and Endocrine Surgery, Department of Surgery, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Axell","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Ku","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Klein","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Fishbein","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado, Aurora, Colorado, USA"},{"name":"Department of Biomedical Informatics, University of Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Annals of Surgical Oncology","first-page":"1444","volume":"20","author":"Fishbein","year":"2013","unstructured":"Fishbein L, Merrill S, Fraker DL, Cohen DL & Nathanson KL. 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(https:\/\/doi.org\/10.1210\/jc.2014-1498)"},{"key":"bib3","series-title":"Pancreas","first-page":"469","article-title":"The North American neuroendocrine tumor society consensus guidelines for surveillance and management of metastatic and\/or unresectable pheochromocytoma and paraganglioma","volume":"50","author":"Fishbein","year":"2021","unstructured":"Fishbein L, Del J, Else T, Howe JR, Asa SL, Cohen DL, Dahia PLM, DL, Goodman KA, Hope TA, et al. The North American neuroendocrine tumor society consensus guidelines for surveillance and management of metastatic and\/or unresectable pheochromocytoma and paraganglioma. Pancreas202150469\u2013493. 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Nature2020 581 434\u2013443."},{"key":"bib6","series-title":"European Journal of Endocrinology","first-page":"771","article-title":"Four novel RET germline variants in exons 8 and 11 display an oncogenic potential in vitro","volume":"162","author":"Muzza","year":"2010","unstructured":"Muzza M, Cordella D, Bombled J, de Paillerets B, Guizzardi F, Francis Z, Beck-Peccoz P, Schlumberger M, Persani L & FugazzolaFour novel RET germline variants in exons 8 and 11 display an oncogenic potential in vitro. European Journal of Endocrinology2010162771\u2013777. (https:\/\/doi.org\/10.1530\/EJE-09-0929)"},{"key":"bib7","series-title":"Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors","first-page":"T1","volume":"25","author":"Wells","year":"2018","unstructured":"Wells SA, Jr. Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors. Endocrine-Related Cancer201825T1\u2013T13. (https:\/\/doi.org\/10.1530\/ERC-17-0325)"},{"key":"bib8","first-page":"1269","volume":"103","author":"Jaber","year":"2018","unstructured":"Jaber T, Hyde SM, Cote GJ, Grubbs EG, Giles WH, Stevens CA & Dadu homozygous RET K666N genotype with an MEN2A phenotype. Journal of Clinical Endocrinology and Metabolism 2018 1031269\u20131272. (https:\/\/doi.org\/10.1210\/jc.2017-02402)"},{"key":"bib9","first-page":"1744","article-title":"Medullary thyroid carcinoma associated with germline RET(K666N) mutation","volume":"26","author":"Xu","year":"2016","unstructured":"Xu JY, Grubbs EG, Waguespack SG, Jimenez C, Gagel RF, Sosa JA, Sellin RV, Dadu R, Hu MI, Trotter CS, et al. Medullary thyroid carcinoma associated with germline RET(K666N) mutation. Thyroid2016261744\u20131751. (https:\/\/doi.org\/10.1089\/thy.2016.0374)"}],"container-title":["Endocrinology, Diabetes & Metabolism Case Reports"],"original-title":[],"link":[{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2024\/3\/EDM24-0009.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2024\/3\/EDM24-0009.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2024\/3\/EDM24-0009.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:48:23Z","timestamp":1784555303000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/edm\/article\/3739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":9,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/edm-24-0009","relation":{},"ISSN":["2052-0573"],"issn-type":[{"value":"2052-0573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,1]]}}}