{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:19:13Z","timestamp":1764260353420,"version":"3.41.2"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32DK007217","U01DK136965","R01DK1015,30","R01DK119955"],"award-info":[{"award-number":["T32DK007217","U01DK136965","R01DK1015,30","R01DK119955"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Germline and somatic pathogenic variants in the CDC73 gene, encoding the nuclear protein parafibromin, increase the risk for parathyroid carcinoma and cause hereditary primary hyperparathyroidism (PHPT) syndromes known as familial isolated hyperparathyroidism (FIHP) and hyperparathyroidism-jaw tumor syndrome (HPT-JT). The identification of pathogenic germline variants in PHPT-susceptibility genes can influence surgical planning for parathyroidectomy, guide screening for potential syndromic manifestations, and identify\/exonerate at-risk family members. Numerous types of pathogenic germline variants have been described for CDC73-related conditions, including deletion, truncating, missense, and splice site mutations. Here, we report identification of a non-coding germline CDC73 variant (CDC73 c.1155-3A\u2009&amp;gt;\u2009G), previously categorized as a variant of uncertain significance (VUS), in a family with HPT-JT. This variant, found in two family members with PHPT, altered CDC73 splicing in peripheral blood cells and disrupted parafibromin immunostaining in associated parathyroid adenomas, strongly evidencing its pathogenicity. Sestamibi scintigraphy yielded nondiagnostic localization results for both patients\u2019 parathyroid adenomas, consistent with prior studies suggesting lower sensitivity for small or cystic lesions. Our findings demonstrate key aspects of CDC73-related disorders, highlight the diagnostic value of RNA testing, and exemplify the importance of obtaining a thorough, three-generational family history.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae149","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T18:17:46Z","timestamp":1732040266000},"source":"Crossref","is-referenced-by-count":1,"title":["<i>CDC73<\/i> c.1155-3A&amp;gt;G is a pathogenic variant that causes aberrant splicing, disrupted parafibromin expression, and hyperparathyroidism-jaw tumor syndrome"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5637-5591","authenticated-orcid":false,"given":"Leor","family":"Needleman","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Stanford University , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolette","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University , Stanford CA 94305 ,","place":["United States"]},{"name":"Stanford Cancer Institute, Stanford University , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sathvika","family":"Sitaraman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Stanford University , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilyn","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Stanford University , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4571-1386","authenticated-orcid":false,"given":"Deborah E","family":"Sellmeyer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Stanford University , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Electron","family":"Kebebew","sequence":"additional","affiliation":[{"name":"Stanford Cancer Institute, Stanford University , Stanford, CA 94305 ,","place":["United States"]},{"name":"Department of Surgery, Stanford University , Stanford CA 94305 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin P","family":"Annes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Stanford University , Stanford, CA 94305 ,","place":["United States"]},{"name":"Stanford Cancer Institute, Stanford University , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"issue":"10116","key":"2024121508000277600_ref1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/S0140-6736(17)31430-7","article-title":"Hyperparathyroidism","volume":"391","author":"Bilezikian","year":"2018","journal-title":"Lancet"},{"issue":"1-2","key":"2024121508000277600_ref2","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s12672-011-0100-8","article-title":"Frequent germ-line mutations of the MEN1, CASR, and HRPT2\/CDC73 genes in young patients with clinically non-familial primary hyperparathyroidism","volume":"3","author":"Starker","year":"2012","journal-title":"Horm Canc"},{"issue":"6","key":"2024121508000277600_ref3","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1111\/joim.12523","article-title":"Genetics of parathyroid 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