{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:27:54Z","timestamp":1789802874614,"version":"4.0.1"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2005,7,12]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Three loci have been shown to be responsible for nonsyndromic familial thoracic aortic aneurysms (TAAs) and aortic dissections (ADs). We recently described a large family in which TAA\/AD associates with patent ductus arteriosus (PDA) and provided genetic arguments for a unique pathophysiological entity.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Genome-wide scan was performed in 40 subjects belonging to 3 generations in this large pedigree. Using the 7 TAA\/AD cases as affected, we observed positive 2-point LOD scores on adjacent markers at chromosome 16p, with a maximum LOD score value of 2.73 at \u03b8=0, a value that increased to 3.56 when 5 PDA cases were included. Multipoint linkage analysis yielded a maximum LOD score of 4.14 in the vicinity of marker\n            <jats:italic>D16S3103<\/jats:italic>\n            . Fine mapping allowed the observation of recombinant haplotypes that delimited a critical 20-cM interval at 16p12.2-p13.13. Automatic determination of aortic compliance with cine MRI showed that all subjects bearing the disease haplotype, even asymptomatic, displayed a very low level of aortic compliance and distensibility. Aortic stiffness was strongly associated with disease haplotype with a marked effect of age, indicating subclinical and early manifestation of the disease.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Genetic analysis of this family identified a unique locus responsible for both TAA\/AD and PDA at chromosome 16p12.2-p13.13 with aortic stiffness as an early hallmark of the disease. TAA\/AD with PDA is a new monogenic entity among the genetically heterogeneous group of TAA\/AD disease.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.104.506345","type":"journal-article","created":{"date-parts":[[2005,7,6]],"date-time":"2005-07-06T03:22:39Z","timestamp":1120620159000},"page":"200-206","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Mapping of Familial Thoracic Aortic Aneurysm\/Dissection With Patent Ductus Arteriosus to 16p12.2\u2013p13.13"],"prefix":"10.1161","volume":"112","author":[{"given":"Philippe Khau","family":"Van Kien","sequence":"first","affiliation":[{"name":"From INSERM U36 and Colle\u0300ge de France; De\u0301partement de Ge\u0301ne\u0301tique, Ho\u0302pital Europe\u0301en Georges Pompidou, Assistance Publique, Ho\u0302pitaux de Paris; and Faculte\u0301 de Me\u0301decine Paris-Descartes, Paris (P.K.V.K., F.M., L.Z., K.J.); Laboratoire de Pharmacologie et de Physiopathologie Cardiovasculaire Expe\u0301rimentale, CHU Dijon, and Universite\u0301 de Bourgogne, Dijon (P.K.V.K., F.B., J.-E.W.); Service de Cardiologie II (P.K.V.K., J.-E.W.) and Centre d\u2019IRM (A.L., F.B.), CHU Dijon, Dijon; and Centre National de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavie","family":"Mathieu","sequence":"additional","affiliation":[{"name":"From INSERM U36 and Colle\u0300ge de France; De\u0301partement de Ge\u0301ne\u0301tique, Ho\u0302pital Europe\u0301en Georges Pompidou, Assistance Publique, Ho\u0302pitaux de Paris; and Faculte\u0301 de Me\u0301decine Paris-Descartes, Paris (P.K.V.K., F.M., L.Z., K.J.); Laboratoire de Pharmacologie et de Physiopathologie Cardiovasculaire Expe\u0301rimentale, CHU Dijon, and Universite\u0301 de Bourgogne, Dijon (P.K.V.K., F.B., J.-E.W.); Service de Cardiologie II (P.K.V.K., J.-E.W.) and Centre d\u2019IRM (A.L., F.B.), CHU Dijon, Dijon; and Centre National de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Zhu","sequence":"additional","affiliation":[{"name":"From INSERM U36 and Colle\u0300ge de France; De\u0301partement de Ge\u0301ne\u0301tique, Ho\u0302pital Europe\u0301en Georges Pompidou, Assistance Publique, Ho\u0302pitaux de Paris; and Faculte\u0301 de Me\u0301decine Paris-Descartes, Paris (P.K.V.K., F.M., L.Z., K.J.); Laboratoire de Pharmacologie et de Physiopathologie Cardiovasculaire Expe\u0301rimentale, CHU Dijon, and Universite\u0301 de Bourgogne, Dijon (P.K.V.K., F.B., J.-E.W.); Service de Cardiologie II (P.K.V.K., J.-E.W.) and Centre d\u2019IRM (A.L., F.B.), CHU Dijon, Dijon; and Centre National de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Lalande","sequence":"additional","affiliation":[{"name":"From INSERM U36 and Colle\u0300ge de France; De\u0301partement de Ge\u0301ne\u0301tique, Ho\u0302pital Europe\u0301en Georges Pompidou, Assistance Publique, Ho\u0302pitaux de Paris; and Faculte\u0301 de Me\u0301decine Paris-Descartes, Paris (P.K.V.K., F.M., L.Z., K.J.); Laboratoire de Pharmacologie et de Physiopathologie Cardiovasculaire Expe\u0301rimentale, CHU Dijon, and Universite\u0301 de Bourgogne, Dijon (P.K.V.K., F.B., J.-E.W.); Service de Cardiologie II (P.K.V.K., J.-E.W.) and Centre d\u2019IRM (A.L., F.B.), CHU Dijon, Dijon; and Centre National de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Betard","sequence":"additional","affiliation":[{"name":"From INSERM U36 and Colle\u0300ge de France; De\u0301partement de Ge\u0301ne\u0301tique, Ho\u0302pital Europe\u0301en Georges Pompidou, Assistance Publique, Ho\u0302pitaux de Paris; and Faculte\u0301 de Me\u0301decine Paris-Descartes, Paris (P.K.V.K., F.M., L.Z., K.J.); Laboratoire de Pharmacologie et de Physiopathologie Cardiovasculaire Expe\u0301rimentale, CHU Dijon, and Universite\u0301 de Bourgogne, Dijon (P.K.V.K., F.B., J.-E.W.); Service de Cardiologie II (P.K.V.K., J.-E.W.) and Centre d\u2019IRM (A.L., F.B.), CHU Dijon, Dijon; and Centre National de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Lathrop","sequence":"additional","affiliation":[{"name":"From INSERM U36 and Colle\u0300ge de France; De\u0301partement de Ge\u0301ne\u0301tique, Ho\u0302pital Europe\u0301en Georges Pompidou, Assistance Publique, Ho\u0302pitaux de Paris; and Faculte\u0301 de Me\u0301decine Paris-Descartes, Paris (P.K.V.K., F.M., L.Z., K.J.); Laboratoire de Pharmacologie et de Physiopathologie Cardiovasculaire Expe\u0301rimentale, CHU Dijon, and Universite\u0301 de Bourgogne, Dijon (P.K.V.K., F.B., J.-E.W.); Service de Cardiologie II (P.K.V.K., J.-E.W.) and Centre d\u2019IRM (A.L., F.B.), CHU Dijon, Dijon; and Centre National de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc\u0327ois","family":"Brunotte","sequence":"additional","affiliation":[{"name":"From INSERM U36 and Colle\u0300ge de France; De\u0301partement de Ge\u0301ne\u0301tique, Ho\u0302pital Europe\u0301en Georges Pompidou, Assistance Publique, Ho\u0302pitaux de Paris; and Faculte\u0301 de Me\u0301decine Paris-Descartes, Paris (P.K.V.K., F.M., L.Z., K.J.); Laboratoire de Pharmacologie et de Physiopathologie Cardiovasculaire Expe\u0301rimentale, CHU Dijon, and Universite\u0301 de Bourgogne, Dijon (P.K.V.K., F.B., J.-E.W.); Service de Cardiologie II (P.K.V.K., J.-E.W.) and Centre d\u2019IRM (A.L., F.B.), CHU Dijon, Dijon; and Centre National de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Eric","family":"Wolf","sequence":"additional","affiliation":[{"name":"From INSERM U36 and Colle\u0300ge de France; De\u0301partement de Ge\u0301ne\u0301tique, Ho\u0302pital Europe\u0301en Georges Pompidou, Assistance Publique, Ho\u0302pitaux de Paris; and Faculte\u0301 de Me\u0301decine Paris-Descartes, Paris (P.K.V.K., F.M., L.Z., K.J.); Laboratoire de Pharmacologie et de Physiopathologie Cardiovasculaire Expe\u0301rimentale, CHU Dijon, and Universite\u0301 de Bourgogne, Dijon (P.K.V.K., F.B., J.-E.W.); Service de Cardiologie II (P.K.V.K., J.-E.W.) and Centre d\u2019IRM (A.L., F.B.), CHU Dijon, Dijon; and Centre National de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Jeunemaitre","sequence":"additional","affiliation":[{"name":"From INSERM U36 and Colle\u0300ge de France; De\u0301partement de Ge\u0301ne\u0301tique, Ho\u0302pital Europe\u0301en Georges Pompidou, Assistance Publique, Ho\u0302pitaux de Paris; and Faculte\u0301 de Me\u0301decine Paris-Descartes, Paris (P.K.V.K., F.M., L.Z., K.J.); Laboratoire de Pharmacologie et de Physiopathologie Cardiovasculaire Expe\u0301rimentale, CHU Dijon, and Universite\u0301 de Bourgogne, Dijon (P.K.V.K., F.B., J.-E.W.); Service de Cardiologie II (P.K.V.K., J.-E.W.) and Centre d\u2019IRM (A.L., F.B.), CHU Dijon, Dijon; and Centre National de..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.134.4.361"},{"key":"e_1_3_3_2_2","first-page":"1287","volume":"56","year":"1995","unstructured":"Francke U, Berg MA, Tynan K, Brenn T, Liu W, Aoyama T, Gasner C, Miller DC, Furthmayr H. 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