{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:21:58Z","timestamp":1761060118570,"version":"3.37.3"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,4,26]],"date-time":"2016-04-26T00:00:00Z","timestamp":1461628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"American College of Medical Genetics"},{"DOI":"10.13039\/100010506","name":"Indiana University Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010506","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":[[2016,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>Marfan syndrome (MFS) and Loeys\u2013Dietz syndrome (LDS) are genetic disorders that affect connective tissue as a result of dysregulated TGF\u2010\u03b2 signaling. MFS is most frequently caused by mutations in <jats:italic>FBN1<\/jats:italic> whereas Loeys\u2013Dietz syndrome results from mutations in <jats:italic>TGFBR1<\/jats:italic> or <jats:italic>TGFBR2<\/jats:italic>. There is substantial inter\u2010 and intra\u2010familial phenotypic variability among these disorders, suggesting the presence of genetic modifiers. Previously, a polymorphism in the TGF\u03b2R1 protein termed the <jats:italic>TGFBR1*6A<\/jats:italic> allele was found to be overrepresented in patients with MFS and was identified as a low penetrance allele with suggestion as a possible modifier. To further investigate the importance of this variant, a retrospective review of genetic and phenotypic findings was conducted for 335 patients evaluated for suspicion of MFS or related disorders. In patients with a diagnosis of MFS, the presence of the <jats:italic>TGFBR1*6A<\/jats:italic> allele was not associated with phenotypic differences. Similarly, careful phenotyping of patients who carried the <jats:italic>TGFBR1*6A<\/jats:italic> allele but did not have MFS did not identify an altered frequency of specific connective tissue features. In this small cohort, the results did not reach significance to identify the <jats:italic>TGFBR1*6A<\/jats:italic> allele as a major modifier for aortic dilation, ectopia lentis, or systemic features associated with MFS or other connective tissue disorders. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37668","type":"journal-article","created":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T03:40:37Z","timestamp":1461728437000},"page":"1786-1790","source":"Crossref","is-referenced-by-count":5,"title":["Analysis of <i>TGFBR1*6A<\/i> variant in individuals evaluated for Marfan syndrome"],"prefix":"10.1002","volume":"170","author":[{"given":"Allyson E.","family":"Somers","sequence":"first","affiliation":[{"name":"University of Cincinnati College of Medicine Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert B.","family":"Hinton","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine Cincinnati Ohio"},{"name":"Division of Cardiology Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Pilipenko","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Miller","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine Cincinnati Ohio"},{"name":"Division of Cardiology Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie M.","family":"Ware","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine Indianapolis 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