{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:26:51Z","timestamp":1791296811608,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2005,7,26]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            A genetic predisposition for progressive enlargement of thoracic aortic aneurysms leading to type A dissection (TAAD) is inherited in an autosomal-dominant manner in up to 19% of patients, and a number of chromosomal loci have been identified for the condition. Having mapped a TAAD locus to 3p24\u201325, we sequenced the gene for transforming growth factor-\u03b2 receptor type II (\n            <jats:italic>TGFBR2<\/jats:italic>\n            ) to determine whether mutations in this gene resulted in familial TAAD.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We sequenced all 8 coding exons of\n            <jats:italic>TGFBR2<\/jats:italic>\n            by using genomic DNA from 80 unrelated familial TAAD cases. We found\n            <jats:italic>TGFBR2<\/jats:italic>\n            mutations in 4 unrelated families with familial TAAD who did not have Marfan syndrome. Affected family members also had descending aortic disease and aneurysms of other arteries. Strikingly, all 4 mutations affected an arginine residue at position 460 in the intracellular domain, suggesting a mutation \u201chot spot\u201d for familial TAAD. Despite identical mutations in the families, assessment of linked polymorphisms suggested that these families were not distantly related. Structural analysis of the TGFBR2 serine\/threonine kinase domain revealed that R460 is strategically located within a highly conserved region of this domain and that the amino acid substitutions resulting from these mutations will interfere with the receptor\u2019s ability to transduce signals.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion\u2014<\/jats:italic>\n            <\/jats:bold>\n            Germline\n            <jats:italic>TGFBR2<\/jats:italic>\n            mutations are responsible for the inherited predisposition to familial TAAD in 5% of these cases. Our results have broad implications for understanding the role of TGF-\u03b2 signaling in the pathophysiology of TAAD.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.105.537340","type":"journal-article","created":{"date-parts":[[2005,7,19]],"date-time":"2005-07-19T00:33:38Z","timestamp":1121733218000},"page":"513-520","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":316,"title":["Mutations in Transforming Growth Factor-\u03b2 Receptor Type II Cause Familial Thoracic Aortic Aneurysms and Dissections"],"prefix":"10.1161","volume":"112","author":[{"given":"Hariyadarshi","family":"Pannu","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Tran","family":"Fadulu","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Chang","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lafont","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumera N.","family":"Hasham","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Sparks","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip F.","family":"Giampietro","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Zaleski","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony L.","family":"Estrera","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazim J.","family":"Safi","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; the Department of Internal Medicine (E.S.), Cardiology Division, The Ohio State University, Columbus; the Department of Medical Genetic Services (P.F.G., C.Z.), Marshfield Clinic, Marshfield, Wis; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Shete","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Institute of Molecular Medicine (H.P., V.T.F., J.C., S.N.H., D.M.M.), the Department of Cardiothoracic and Vascular Surgery (A.L.E., H.J.S.), and the Structural Biology Research Center (C.S.R.), the University of Texas Health Science Center at Houston; 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