{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:27:20Z","timestamp":1791296840581,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T00:00:00Z","timestamp":1355356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dilation or aneurysm of the ascending aorta can progress to acute aortic dissection (Thoracic Aortic Aneurysms and Aortic Dissections, TAAD). Mutations in genes encoding TGF\u2010\u03b2\u2010related proteins (<jats:italic>TGFBR1<\/jats:italic>, <jats:italic>TGFBR2<\/jats:italic>, <jats:italic>FBN1<\/jats:italic>, and <jats:italic>SMAD3<\/jats:italic>) cause syndromic and inherited TAAD. <jats:italic>SMAD4<\/jats:italic> mutations are associated with juvenile polyposis syndrome (JPS) and a combined JPS\u2013hereditary hemorrhagic telangiectasia (HHT) known as JPS\u2013HHT. A family with JPS\u2013HHT was reported to have aortic root dilation and mitral valve abnormalities. We report on two patients with JPS\u2013HHT with <jats:italic>SMAD4<\/jats:italic> mutations associated with thoracic aortic disease. The first patient, an 11\u2010year\u2010old boy without Marfan syndrome features, had JPS and an apparently de novo <jats:italic>SMAD4<\/jats:italic> mutation (c.1340_1367dup28). Echocardiography showed mild dilation of the aortic annulus and aortic root, and mild dilation of the sinotubular junction and ascending aorta. Computed tomography confirmed aortic dilation and showed small pulmonary arteriovenous malformations (PAVM). The second patient, a 34\u2010year\u2010old woman with colonic polyposis, HHT, and features of Marfan syndrome, had a <jats:italic>SMAD4<\/jats:italic> mutation (c.1245_1248delCAGA). Echocardiography showed mild aortic root dilation. She also had PAVM and hepatic focal nodular hyperplasia. Her family history was significant for polyposis, HHT, thoracic aortic aneurysm, and dissection and skeletal features of Marfan syndrome in her father. These two cases confirm the association of thoracic aortic disease with JPS\u2013HHT resulting from <jats:italic>SMAD4<\/jats:italic> mutations. We propose that the thoracic aorta should be screened in patients with <jats:italic>SMAD4<\/jats:italic> mutations to prevent untimely death from dissection. This report also confirms that <jats:italic>SMAD4<\/jats:italic> mutations predispose to TAAD. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35659","type":"journal-article","created":{"date-parts":[[2012,12,14]],"date-time":"2012-12-14T05:09:24Z","timestamp":1355461764000},"page":"185-191","source":"Crossref","is-referenced-by-count":59,"title":["Thoracic aortic disease in two patients with juvenile polyposis syndrome and <i>SMAD4<\/i> mutations"],"prefix":"10.1002","volume":"161","author":[{"given":"Polakit","family":"Teekakirikul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianna M.","family":"Milewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald 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