{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:58:41Z","timestamp":1783569521350,"version":"3.55.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Familial Cancer"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Serrated Polyposis Syndrome (SPS) is characterized by multiple and\/or large serrated polyps in the colon and an increased risk of colorectal cancer (CRC). The etiology is largely unknown, but in a subset of patients with SPS, monoallelic pathogenic variants in <jats:italic>RNF43<\/jats:italic> are detected. To date, however, the penetrance and phenotypic spectrum of patients carrying pathogenic variants (PV) in <jats:italic>RNF43<\/jats:italic> are poorly described. We present eight patients both with and without serrated polyps from four unrelated families with likely pathogenic variants (LPV) in <jats:italic>RNF43<\/jats:italic> and compare the results to current literature. The patients were referred to genetic counseling due to suspicion of hereditary cancer. They underwent genetic testing with custom NGS gene panels including <jats:italic>RNF43<\/jats:italic> as part of a routine genetic work-up. Three LPVs, one multi-exon deletion and two nonsense variants, were detected in four families. Family I had a history of CRC and serrated polyps, but in the three other families (II\u2012IV) there was no history of CRC or serrated polyps. Colonoscopies in the probands of these families did not reveal any serrated polyps and\/or CRC despite some of them being relatively old. Our findings suggest that the penetrance of <jats:italic>RNF43<\/jats:italic>-related disease is much lower than previously thought, and raise questions about the connection between <jats:italic>RNF43<\/jats:italic> and disease. The results highlight the complexity of genetic counseling in <jats:italic>RNF43<\/jats:italic> positive families\u2013 particularly in families without polyposis. Further research is needed to elucidate the role of <jats:italic>RNF43<\/jats:italic> in the risk of SPS and CRC.<\/jats:p>","DOI":"10.1007\/s10689-024-00428-6","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T05:53:25Z","timestamp":1731650005000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Germline pathogenic variants in RNF43 in patients with and without serrated polyposis syndrome"],"prefix":"10.1007","volume":"24","author":[{"given":"Heidi Hessel\u00f8","family":"Brinch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Byrjalsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Lohse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas \u00d8rslev","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G\u00e1sdal","family":"Karstensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta Schlott","family":"Kristiansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie","family":"Jelsig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"issue":"1","key":"428_CR1","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1136\/gutjnl-2018-318134","volume":"69","author":"AG Bleijenberg","year":"2020","unstructured":"Bleijenberg AG, JE IJ, van Herwaarden YJ, Carballal S, Pellis\u00e9 M, Jung G et al (2020) Personalised surveillance for serrated polyposis syndrome: results from a prospective 5-year international cohort study. 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