{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:37:47Z","timestamp":1783633067087,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Diagnostic germline <jats:italic>RET<\/jats:italic> analysis is offered to all patients with a diagnosis of medullary thyroid carcinoma (MTC), or other conditions associated with multiple endocrine neoplasia type 2 (MEN2) in the United Kingdom. Here, we report the experience of a single centre's germline <jats:italic>RET<\/jats:italic> analysis over a 21\u2010year period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective case\u2010note review.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>All index patients referred to the Exeter Genomics Laboratory for diagnostic germline <jats:italic>RET<\/jats:italic> analysis between 1997 and 2018, and unaffected family members, undergoing predictive testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>The rate and nature of pathogenic variant detection were recorded, as well as the indication for testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>1,058 index patients and 551 unaffected family members were tested. The overall rate of pathogenic variant detection was 10.2% amongst index patients and 29% amongst unaffected family members. The commonest indication was isolated MTC, and amongst the 690 patients with isolated MTC, 68 (9.9%) were found to harbour a <jats:italic>RET<\/jats:italic> pathogenic variant. Of those with presumed sporadic MTC, 8.5% were found to harbour germline <jats:italic>RET<\/jats:italic> pathogenic variants, compared with 36.4% of those with a family history of MEN2\u2010associated conditions. Pathogenic variants were identified in 3.6% and 0% of patients with isolated phaeochromocytoma and primary hyperparathyroidism, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although the detection rate of <jats:italic>RET<\/jats:italic> germline pathogenic variants in patients with presumed sporadic MTC was significant, the overall detection rate in those with MTC was lower than expected in this series. Advances in <jats:italic>RET<\/jats:italic> analysis in response to reports of new variants over the last two decades are likely to have improved the pick\u2010up rate in recent years.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14395","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T19:44:52Z","timestamp":1608407092000},"page":"295-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Diagnostic <i>RET<\/i> genetic testing in 1,058 index patients: A UK centre perspective"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9971-4334","authenticated-orcid":false,"given":"Jonathan Mark","family":"Fussey","sequence":"first","affiliation":[{"name":"Department of Head and Neck Surgery Royal Devon and Exeter Hospital Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel 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