{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:03:21Z","timestamp":1778817801187,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,29]],"date-time":"2013-03-29T00:00:00Z","timestamp":1364515200000},"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":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Recently, mutations in the <jats:italic>SMAD3<\/jats:italic> gene were found to cause a new autosomal dominant aneurysm condition similar to Loeys\u2013Dietz syndrome (LDS), mostly with osteoarthritis, called aneurysms\u2013osteoarthritis syndrome (AOS). Our 3\u2010year\u2010old propositus underwent correction of an inguinal hernia at 3 months and substitution of the ascending aorta for pathologic dilation at 12 months of age. Family history reveals aortic dilation in his mother at 30 years, death due to aortic dissection of an 18\u2010year\u2010old maternal aunt, surgical replacement of the ascending aorta because of aneurysm in a maternal uncle at 19 years, postpartum death of the maternal grandmother at 24 years and surgical intervention because of thoracic aortic aneurysm in a brother of the propositus' grandmother at 54 years. The affected individuals present with several other signs of connective tissue disease, but the two adult patients evaluated revealed no radiologic evidence of osteoarthritis. Molecular testing of the <jats:italic>TGFBR1<\/jats:italic> and <jats:italic>TGFBR2<\/jats:italic> genes, involved in LDS, resulted negative, but analysis of <jats:italic>SMAD3<\/jats:italic> disclosed the novel heterozygous loss\u2010of\u2010function mutation c.1170_1179del (p.Ser391AlafsX7) in exon 9 in all affected family members, confirming the diagnosis of AOS. <jats:italic>SMAD3<\/jats:italic> mutations should be considered in patients of all ages with LDS\u2010like phenotypes and negative <jats:italic>TGFBR1\/2<\/jats:italic> molecular tests, especially in the presence of aortic root or ascending aortic aneurysms, even though signs of early onset osteoarthritis are absent. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.35852","type":"journal-article","created":{"date-parts":[[2013,3,29]],"date-time":"2013-03-29T18:31:06Z","timestamp":1364581866000},"page":"1028-1035","source":"Crossref","is-referenced-by-count":59,"title":["Thoracic Aortic Aneurysm in Infancy in Aneurysms\u2013<scp>O<\/scp>steoarthritis Syndrome Due to a Novel <scp><i>SMAD<\/i><\/scp><i>3<\/i> Mutation: Further Delineation of the Phenotype"],"prefix":"10.1002","volume":"161","author":[{"given":"Anita","family":"Wischmeijer","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Policlinico Sant'Orsola\u2010Malpighi, University of Bologna Bologna Italy"},{"name":"Clinical Genetics Unit Istituto di Ricovero e Cura a Carattere Scientifico, Arcispedale S. 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