{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:32:19Z","timestamp":1783632739966,"version":"3.55.0"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Homozygous mutations, 2 identical gene versions (alleles), 1 from each biological parent, are exceptional. Clinical descriptions of affected families, comprising few carriers only, are scattered throughout the literature, hindering evidence generation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Included in this literature analysis were 5 RET families with \u22651 homozygous carrier and \u22653 heterozygous carriers per family.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In consanguineous families with first-degree cousins, homozygotes presented with node-positive medullary thyroid cancer and pheochromocytoma in their mid-teens, whereas heterozygotes presented in their end-30s and early 40s. Homozygotes developed node-positive medullary thyroid cancer 27.4 years and pheochromocytoma 23 years earlier than heterozygotes. These age differences were smaller in the 15 families carrying founder mutation p.Leu666delinsAsnSer, whereas homozygotes developed node-positive medullary thyroid cancer in their mid-40s, 6 years earlier than heterozygotes in their early 50s.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These results, limited in scope and size and modulated by extent of consanguinity, are consistent with moderate dose\u2013response effects accelerating MEN2A development.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae025","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T13:16:17Z","timestamp":1710162977000},"page":"K43-K46","source":"Crossref","is-referenced-by-count":8,"title":["Accelerated MEN2A in homozygous RET carriers in the context of consanguinity"],"prefix":"10.1093","volume":"190","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6796-079X","authenticated-orcid":false,"given":"Andreas","family":"Machens","sequence":"first","affiliation":[{"name":"Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg , Ernst-Grube-Str. 40, D-06097 Halle (Saale) , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Dralle","sequence":"additional","affiliation":[{"name":"Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg , Ernst-Grube-Str. 40, D-06097 Halle (Saale) , Germany"},{"name":"Department of General, Visceral and Transplantation Surgery, Division of Endocrine Surgery, University of Duisburg-Essen , D-45122 Essen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"issue":"6","key":"2024032819001414800_lvae025-B1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1089\/thy.2014.0335","article-title":"Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma","volume":"25","author":"Wells","year":"2015","journal-title":"Thyroid"},{"issue":"6","key":"2024032819001414800_lvae025-B2","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/humu.23430","article-title":"Genotype-specific progression of hereditary medullary thyroid cancer","volume":"39","author":"Machens","year":"2018","journal-title":"Hum Mutat"},{"issue":"2","key":"2024032819001414800_lvae025-B3","doi-asserted-by":"crossref","first-page":"104141","DOI":"10.1016\/j.ejmg.2021.104141","article-title":"Homozygosity for the pathogenic RET hotspot variant p.Cys634Trp: a consanguineous family with 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disease only in the homozygous gene carriers","volume":"131","author":"Lecube","year":"2002","journal-title":"Surgery"},{"issue":"3","key":"2024032819001414800_lvae025-B7","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/ejendo\/lvad126","article-title":"Germline founder variant c.1998delinsTTCT in the RET oncogene: a cohort study in 15 Belgian families","volume":"189","author":"Vuylsteke","year":"2023","journal-title":"Eur J Endocrinol"},{"issue":"11","key":"2024032819001414800_lvae025-B8","doi-asserted-by":"crossref","first-page":"5823","DOI":"10.1210\/jc.2004-0312","article-title":"Identification of a novel point mutation in the RET gene (Ala883Thr), which is associated with medullary thyroid carcinoma phenotype only in homozygous condition","volume":"89","author":"Elisei","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2024032819001414800_lvae025-B9","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1210\/jc.2017-02402","article-title":"A homozygous RET K666N genotype with an MEN2A phenotype","volume":"103","author":"Jaber","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2024032819001414800_lvae025-B10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/j.1469-1809.1996.tb01171.x","article-title":"Autosomal recessive disorders in Saguenay-Lac-Saint-Jean (Quebec, Canada): a study of inbreeding","volume":"60","author":"De Braekeleer","year":"1996","journal-title":"Ann Hum Genet"},{"issue":"4","key":"2024032819001414800_lvae025-B11","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/ahg.12308","article-title":"Consanguinity: a blessing or menace at population level?","volume":"83","author":"Bhinder","year":"2019","journal-title":"Ann Hum 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