{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:13:43Z","timestamp":1788779623041,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Backgrounds<\/jats:title><jats:p><jats:italic>MUTYH<\/jats:italic>\u2010associated polyposis (MAP) is an autosomal recessive disease caused by biallelic pathogenic variants (PV) of the <jats:italic>MUTYH<\/jats:italic> gene. The aim of this study was to investigate the genetic causes of unexplained polyposis patients with monoallelic <jats:italic>MUTYH<\/jats:italic> PV. The analysis focused on 26 patients with suspected MAP, belonging to 23 families. Ten probands carried also one or more additional <jats:italic>MUTYH<\/jats:italic> variants of unknown significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Based on variant type and on the collected clinical and molecular data, these variants were reinterpreted by applying the ACMG\/AMP rules. Moreover, supplementary analyses were carried out to investigate the presence of other variants and copy number variations in the coding and promoter regions of <jats:italic>MUTYH<\/jats:italic>, as well as other polyposis genes <jats:italic>(APC<\/jats:italic>, <jats:italic>NTHL1<\/jats:italic>, <jats:italic>POLE<\/jats:italic>, <jats:italic>POLD1<\/jats:italic>, <jats:italic>MSH3<\/jats:italic>, <jats:italic>RNF43<\/jats:italic>, and <jats:italic>MCM9<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We reclassified 4 out of 10 <jats:italic>MUTYH<\/jats:italic> variants as pathogenic or likely pathogenic, thus supporting the diagnosis of MAP in only four cases. Two other patients belonging to the same family showed a previously undetected deletion of the <jats:italic>APC<\/jats:italic> gene promoter. No PVs were found in the other investigated genes. However, 6 out of the 18 remaining families are still interesting MAP candidates, due to the co\u2010presence of a class 3 <jats:italic>MUTYH<\/jats:italic> variant that could be reinterpreted in the next future.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Several efforts are necessary to fully elucidate the genetic etiology of suspected MAP patients, especially those with the most severe polyposis\/tumor phenotype. Clinical data, tumor molecular profile, family history, and polyposis inheritance mode may guide variant interpretation and address supplementary studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1831","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T06:47:30Z","timestamp":1635317250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Filling the gap: A thorough investigation for the genetic diagnosis of unsolved polyposis patients with monoallelic <i>MUTYH<\/i> pathogenic variants"],"prefix":"10.1002","volume":"9","author":[{"given":"Anastasia","family":"Dell\u2019Elice","sequence":"first","affiliation":[{"name":"Unit of Functional Oncogenomics and Genetics Centro di Riferimento Oncologico di Aviano (CRO) IRCCS Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Cini","sequence":"additional","affiliation":[{"name":"Unit of Functional Oncogenomics and Genetics Centro di Riferimento Oncologico di Aviano (CRO) IRCCS Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Fornasarig","sequence":"additional","affiliation":[{"name":"Unit of Oncologic Gastroenterology Centro di Riferimento Oncologico di Aviano (CRO) IRCCS Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Armelao","sequence":"additional","affiliation":[{"name":"U.O. 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