{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T15:05:15Z","timestamp":1774969515524,"version":"3.50.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Thoracic aortic aneurysm (TAA) is a common progressive disorder involving gradual dilation of the ascending and\/or descending thoracic aorta that eventually leads to dissection or rupture. Nonsydromic TAA can occur as a genetically triggered, familial disorder that is usually transmitted in a monogenic autosomal dominant fashion and is known as familial TAA. Genetic analyses of families affected with TAA have identified several chromosomal loci, and further mapping of familial TAA genes has highlighted disease-causing mutations in at least 4 genes: myosin heavy chain 11 (\n              <jats:italic>MYH11)<\/jats:italic>\n              , \u03b1-smooth muscle actin (\n              <jats:italic>ACTA2)<\/jats:italic>\n              , and transforming growth factor \u03b2 receptors I and II (\n              <jats:italic>TGF\u03b2RI<\/jats:italic>\n              and\n              <jats:italic>TGF\u03b2RII<\/jats:italic>\n              ).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We evaluated 100 probands to determine the mutation frequency in\n              <jats:italic>MYH11<\/jats:italic>\n              ,\n              <jats:italic>ACTA2<\/jats:italic>\n              ,\n              <jats:italic>TGF\u03b2RI<\/jats:italic>\n              , and\n              <jats:italic>TGF\u03b2RII<\/jats:italic>\n              in an unbiased population of individuals with genetically mediated TAA. In this study, 9% of patients had a mutation in one of the genes analyzed, 3% of patients had mutations in\n              <jats:italic>ACTA2<\/jats:italic>\n              , 3% in\n              <jats:italic>MYH11<\/jats:italic>\n              , 1% in\n              <jats:italic>TGF\u03b2RII<\/jats:italic>\n              , and no mutations were found in\n              <jats:italic>TGF\u03b2RI.<\/jats:italic>\n              Additionally, we identified mutations in a 75 base pair alternatively spliced\n              <jats:italic>TGF\u03b2RII<\/jats:italic>\n              exon, exon 1a that produces the TGF\u03b2RIIb isoform and accounted for 2% of patients with mutations. Our in vitro analyses indicate that the\n              <jats:italic>TGF\u03b2RIIb<\/jats:italic>\n              activating mutations alter receptor function on TGF\u03b22 signaling.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              We propose that TGF\u03b2RIIb expression is a regulatory mechanism for TGF\u03b22 signal transduction. Dysregulation of the TGF\u03b22 signaling pathway, as a consequence of\n              <jats:italic>TGF\u03b2RIIb<\/jats:italic>\n              mutations, results in aortic aneurysm pathogenesis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.112.964064","type":"journal-article","created":{"date-parts":[[2012,10,26]],"date-time":"2012-10-26T00:31:39Z","timestamp":1351211499000},"page":"621-629","source":"Crossref","is-referenced-by-count":16,"title":["<i>TGF\u03b2RIIb<\/i>\n            Mutations Trigger Aortic Aneurysm Pathogenesis by Altering Transforming Growth Factor \u03b22 Signal Transduction"],"prefix":"10.1161","volume":"5","author":[{"given":"Katharine J.","family":"Bee","sequence":"first","affiliation":[{"name":"From the Center for Molecular Cardiology, Greenberg Division of Cardiology, Weill Cornell Medical College, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Wilkes","sequence":"additional","affiliation":[{"name":"From the Center for Molecular Cardiology, Greenberg Division of Cardiology, Weill Cornell Medical College, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard B.","family":"Devereux","sequence":"additional","affiliation":[{"name":"From the Center for Molecular Cardiology, Greenberg Division of Cardiology, Weill Cornell Medical College, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig T.","family":"Basson","sequence":"additional","affiliation":[{"name":"From the Center for Molecular Cardiology, Greenberg Division of Cardiology, Weill Cornell Medical College, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathy J.","family":"Hatcher","sequence":"additional","affiliation":[{"name":"From the Center for Molecular Cardiology, Greenberg Division of Cardiology, Weill Cornell Medical College, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.134.4.361"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.5.1229"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000017473.78775.f6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2006.04.098"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(10)60825-X"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.120.suppl_18.S540"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1721"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000078634.33124.95"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.537340"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.6"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.10.006"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.744"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.20.2469"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.20.2461"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.753"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000151766"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.308"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1996.0066"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1385\/1-59259-038-1:857","volume-title":"In: The Nucleic Acids Protocols Handbook","author":"Pogulis RJ","year":"2000","unstructured":"Pogulis RJ, Vallejo AN, Pease LR. , Rapley R. 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