{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:27:15Z","timestamp":1791296835454,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,5,5]],"date-time":"2015-05-05T00:00:00Z","timestamp":1430784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013213","name":"ARUP Institute for Clinical and Experimental Pathology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013213","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec><jats:label\/><jats:p>Aortopathy can be defined as aortic dilation, aneurysm, dissection, and tortuosity. Familial aortopathy may occur secondary to fibrillin\u20101 (<jats:italic>FBN1<\/jats:italic>) mutations in the setting of Marfan syndrome, or may occur as a result of other genetic defects with different, but occasionally overlapping, phenotypes. Because of the phenotypic overlap and genetic heterogeneity of disorders featuring aortopathy, we developed a next generation sequencing (NGS) assay and comparative genomic hybridization (CGH) array to detect mutations in 10 genes that cause thoracic aortic aneurysms (TAAs). Here, we report on the clinical and molecular findings in 175 individuals submitted for aortopathy panel testing at ARUP laboratories. Ten genes associated with heritable aortopathies were targeted using hybridization capture prior to sequencing. NGS results were analyzed, and variants were confirmed using Sanger sequencing. Array CGH was used to detect copy\u2010number variation. Of 175 individuals, 18 had a pathogenic mutation and 32 had a variant of uncertain significance (VUS). Most pathogenic mutations (72%) were identified in<jats:italic>FBN1<\/jats:italic>. A novel large<jats:italic>SMAD3<\/jats:italic>duplication and<jats:italic>FBN1<\/jats:italic>deletion were identified. Over half who had TAAs or other aortic involvement tested negative for a mutation, suggesting that additional aortopathy genes exist. We anticipate that the clinical sensitivity of at least 10.3% will rise with VUS reclassification and as additional genes are identified and included in the panel. The aortopathy NGS panel aids in the timely molecular diagnosis of individuals with disorders featuring aortopathy and guides proper treatment. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37085","type":"journal-article","created":{"date-parts":[[2015,5,5]],"date-time":"2015-05-05T22:47:31Z","timestamp":1430866051000},"page":"1747-1757","source":"Crossref","is-referenced-by-count":58,"title":["Clinical utility of a next generation sequencing panel assay for Marfan and Marfan\u2010like syndromes featuring aortopathy"],"prefix":"10.1002","volume":"167","author":[{"given":"Whitney","family":"Wooderchak\u2010Donahue","sequence":"first","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"},{"name":"Department of Pathology University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"VanSant\u2010Webb","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Tvrdik","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parker","family":"Plant","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Lewis","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Stocks","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Raney","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Meyers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Medical Genetics University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alizabeth","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Medical Genetics University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan F.","family":"Rope","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kaiser Permanente Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anji T.","family":"Yetman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Cardiology University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B.","family":"Bleyl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Cardiology University of Utah Salt Lake City Utah"},{"name":"Clinical Genetics Institute Intermountain Healthcare Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Mesley","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Cardiothoracic Surgery University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bull","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Cardiothoracic Surgery University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Thomas","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Internal Medicine Cardiology Division Arkansas Children's Hospital Little Rock Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayra Martinez","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Department of Cardiology Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Cardiology Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Lacro","sequence":"additional","affiliation":[{"name":"Department of Cardiology Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Woerner","sequence":"additional","affiliation":[{"name":"Division of Genetics Boston 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