{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T05:32:29Z","timestamp":1771651949922,"version":"3.50.1"},"reference-count":10,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,25]],"date-time":"2023-12-25T00:00:00Z","timestamp":1703462400000},"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":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Juvenile Polyposis Syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple hamartomatous gastrointestinal polyps. Here, we present a case of JPS with a mosaic variant in SMAD4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exome sequencing TRIO analysis, using germline DNA from the biological mother and father along with the index case (IC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 46\u2010year\u2010old male with no family history of cancer presented with chronic iron deficiency anemia and was diagnosed with massive gastric polyposis (\u2265100 polyps). At the age of 59, he underwent a total gastrectomy, revealing numerous polyps occupying the entire gastric mucosa, including a 5\u2009cm gastric hyperplastic polyp with high\u2010grade dysplasia and focal adenocarcinoma. TRIO analysis identified the c.386A&gt;C p.(Asn129Thr) variant in the SMAD4 gene at an allele frequency (AF) of 22%, suggesting its mosaic origin. Subsequently, the variant was found in heterozygosity in the IC's son, who exhibited two subcentimeter polyps in the colon and seven inflammatory gastric polyps with gastric inflammatory areas and hyperplasia, suggesting that the c.386A&gt;C p.(Asn129Thr) variant in SMAD4 segregated with the phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study provides evidence supporting the classification of the c.386A&gt;C p.(Asn129Thr) variant in SMAD4 as a likely pathogenic variant. This finding contributes to improved accuracy in the diagnosis and genetic counseling of JPS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2348","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T06:03:51Z","timestamp":1703570631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The c.386A&gt;C p.(Asn129Thr) variant in <scp>SMAD4<\/scp> is likely to be pathogenic, causing Juvenile Polyposis Syndrome. A case report of a mosaic variant"],"prefix":"10.1002","volume":"12","author":[{"given":"F\u00e1tima","family":"Valent\u00edn","sequence":"first","affiliation":[{"name":"Gastroenterology and Hepatology Department Endoscopy Unit Puerta de Hierro University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto Herreros","family":"de Tejada","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department Endoscopy Unit Puerta de Hierro University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emiliano","family":"Gonzal\u00e9z\u2010Vioque","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit, Laboratory Medicine Department Puerta de Hierro University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Garc\u00eda\u2010Sim\u00f3n","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit, Laboratory Medicine Department Puerta de Hierro University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Hereditary Cancer Unit, Medical Oncology Department Puerta de Hierro University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1634-7397","authenticated-orcid":false,"given":"Atocha","family":"Romero","sequence":"additional","affiliation":[{"name":"Hereditary Cancer Unit, Medical Oncology Department Puerta de Hierro University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0826-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.02.021"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01091.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2005.03865.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37093"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-2980.13029"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/DCR.0b013e31825aad32"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2014.435"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.23230"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2348","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T12:27:42Z","timestamp":1706531262000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,25]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/mgg3.2348"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2348","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,25]]},"assertion":[{"value":"2023-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2348"}}