{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:26:50Z","timestamp":1789738010050,"version":"4.0.1"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,7]],"date-time":"2016-02-07T00:00:00Z","timestamp":1454803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"American Heart Association Innovative Research","award":["14IRG18830027"],"award-info":[{"award-number":["14IRG18830027"]}]},{"name":"Burroughs Wellcome Fund Clinical Scientist","award":["#1008496"],"award-info":[{"award-number":["#1008496"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:label\/><jats:p>Thoracic aortic aneurysm (TAA) is a genetically heterogeneous disease involving subclinical and progressive dilation of the thoracic aorta, which can lead to life\u2010threatening complications such as dissection or rupture. Genetic testing is important for risk stratification and identification of at risk family members, and clinically available genetic testing panels have been expanding rapidly. However, when past testing results are normal, there is little evidence to guide decision\u2010making about the indications and timing to pursue additional clinical genetic testing. Results from research based genetic testing can help inform this process. Here we present 10 TAA patients who have a family history of disease and who enrolled in research\u2010based exome testing. Nine of these ten patients had previous clinical genetic testing that did not identify the cause of disease. We sought to determine the number of rare variants in 23 known TAA associated genes identified by research\u2010based exome testing. In total, we found 10 rare variants in six patients. Likely pathogenic variants included a <jats:italic>TGFB2<\/jats:italic> variant in one patient and a <jats:italic>SMAD3<\/jats:italic> variant in another. These variants have been reported previously in individuals with similar phenotypes. Variants of uncertain significance of particular interest included novel variants in <jats:italic>MYLK<\/jats:italic> and <jats:italic>MFAP5<\/jats:italic>, which were identified in a third patient. In total, clinically reportable rare variants were found in 6\/10 (60%) patients, with at least 2\/10 (20%) patients having likely pathogenic variants identified. These data indicate that consideration of re\u2010testing is important in TAA patients with previous negative or inconclusive results. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37568","type":"journal-article","created":{"date-parts":[[2016,2,8]],"date-time":"2016-02-08T01:11:18Z","timestamp":1454893878000},"page":"1288-1294","source":"Crossref","is-referenced-by-count":25,"title":["Clinically relevant variants identified in thoracic aortic aneurysm patients by research exome sequencing"],"prefix":"10.1002","volume":"170","author":[{"given":"Jeffrey A.","family":"Schubert","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics Biochemistry and Microbiology University of Cincinnati College of Medicine Cincinnati Ohio"},{"name":"Department of Pediatrics and Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Landis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R.","family":"Shikany","sequence":"additional","affiliation":[{"name":"Division of Cardiology Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Hinton","sequence":"additional","affiliation":[{"name":"Division of Cardiology Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Ware","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Biochemistry and Microbiology University of Cincinnati College of Medicine Cincinnati Ohio"},{"name":"Department of Pediatrics and Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2006.04.098"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.01.040"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2348"},{"key":"e_1_2_6_5_1","unstructured":"Exome Aggregation Consortium. Analysis of protein\u2010coding genetic variation in 60 706 humans2015.http:\/\/exac.broadinstitute.org\/"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.300675"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e3181d4739e"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/504304"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-012-0241-4"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/HCO.0000000000000114"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.02.042"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.03.011"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2349"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.8.080706.092303"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2013.06.004"},{"key":"e_1_2_6_16_1","first-page":"271","article-title":"The genetics and genomics of thoracic aortic disease","volume":"2","author":"Pomianowski P","year":"2013","journal-title":"Ann Cardiothorac Surg"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2011.08.079"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2012.09.029"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.744"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100382"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0010064"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37568","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37568","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T08:16:31Z","timestamp":1696580191000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,7]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1002\/ajmg.a.37568"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37568","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,7]]}}}