{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:46:53Z","timestamp":1771912013795,"version":"3.50.1"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ministere de l'enseignement superieur Tunisie"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Colorectal cancer (CRC) is among the most commonly diagnosed cancers worldwide, with 2% to 5% of cases being linked to inherited syndromes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Material and methods<\/jats:title>\n<jats:p>A cohort of 30 Tunisian patients was selected and divided into two groups based on clinical features and family history: Group 1 included patients clinically diagnosed with hereditary polyposis syndromes, including MUTYH-Associated Polyposis (MAP: 15 cases) and Familial Adenomatous Polyposis (FAP: 5 cases). Group 2 consisted of patients clinically diagnosed with non-polyposis syndromes, including Lynch Syndrome (LS: 7 cases) and other rare syndromes (OS: 3 cases). Genetic testing was performed using either Sanger sequencing or targeted next-generation sequencing (NGS) with a cancer panel including 31 cancer-related genes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In Group 1, MAP was confirmed in 13 patients who were homozygous carriers of the pathogenic variant (c.1143_1144dup p.Glu382fs) in the <jats:italic>MUTYH<\/jats:italic> gene. For patients suspected of having FAP, pathogenic variants in the <jats:italic>APC<\/jats:italic> gene were identified in only two patients (c.3183_3187del p.Lys1061_Gln1062insTer, and c.2016_2017del p.His672Ter), while another patient carried a frameshift variant (c.502_503del, p.Ile168SerTer11) in the <jats:italic>PTEN<\/jats:italic> gene, indicating Cowden Syndrome. In Group 2, genetic testing confirmed Peutz-Jeghers Syndrome in a young girl who had a large deletion in the <jats:italic>STK11<\/jats:italic> gene. For patients suspected to have LS, only variants of unknown significance (VUS) were identified in MMR. Further genetic investigations are required to identify the pathogenic variant in these patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Overall, our results highlight the importance of genetic testing to better understand hereditary CRC syndromes in Tunisian families, and to improve the management of patients and their relatives.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0326343","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T17:27:21Z","timestamp":1750786041000},"page":"e0326343","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic profiling of inherited colorectal cancer syndromes in Tunisian 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