{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T03:43:40Z","timestamp":1768535020035,"version":"3.49.0"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T00:00:00Z","timestamp":1425340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD064667"],"award-info":[{"award-number":["R01 HD064667"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R25 GM056929-16"],"award-info":[{"award-number":["R25 GM056929-16"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 HG006542"],"award-info":[{"award-number":["U54 HG006542"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Congenital diaphragmatic hernia (CDH) is a relatively common, life\u2010threatening birth defect. We present a family with recurrent CDH\u2014paraesophageal and central\u2014for whom exome sequencing (ES) revealed a frameshift mutation (c.4969_4970insA, p.Ile1657Asnfs*30) in the fibrillin 1 gene (<jats:italic>FBN1<\/jats:italic>) that causes Marfan syndrome. A diagnosis of Marfan syndrome had not been considered previously in this family. However, a review of the literature demonstrated that <jats:italic>FBN1<\/jats:italic> mutations have an unusual pattern of CDH in which paraesophageal hernias are particularly common. Subsequent clinical evaluations revealed evidence for ectopia lentis in affected family members supporting a clinical diagnosis of Marfan syndrome. Since only two other cases of familial CDH have been described in association with <jats:italic>FBN1<\/jats:italic> mutations, we investigated an oligogenic hypothesis by examining ES data for deleterious sequence changes in other CDH\u2010related genes. This search revealed putatively deleterious sequence changes in four other genes that have been shown to cause diaphragm defects in humans and\/or mice\u2014<jats:italic>FREM1<\/jats:italic>, <jats:italic>DES<\/jats:italic>, <jats:italic>PAX3<\/jats:italic> and <jats:italic>MET<\/jats:italic>. It is unclear whether these changes, alone or in aggregate, are contributing to the development of CDH in this family. However, their individual contribution is likely to be small compared to that of the frameshift mutation in <jats:italic>FBN1<\/jats:italic>. We conclude that ES can be used to identify both major and minor genetic factors that may contribute to CDH. These results also suggest that ES should be considered in the diagnostic evaluation of individuals and families with CDH, particularly when other diagnostic modalities have failed to reveal a molecular etiology. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36960","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T12:31:25Z","timestamp":1425385885000},"page":"831-836","source":"Crossref","is-referenced-by-count":23,"title":["<i>FBN1<\/i> contributing to familial congenital diaphragmatic hernia"],"prefix":"10.1002","volume":"167","author":[{"given":"Tyler F.","family":"Beck","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe M.","family":"Campeau","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine 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