{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:15:01Z","timestamp":1790640901392,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,11,19]],"date-time":"2012-11-19T00:00:00Z","timestamp":1353283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that causes high newborn mortality. Isolated or non\u2010syndromic CDH is considered a multifactorial disease, with strong evidence implicating genetic factors. As low heritability has been reported in isolated CDH, family\u2010based genetic methods have yet to identify the genetic factors associated with the defect. Using the Utah Population Database, we identified distantly related patients from several extended families with a high incidence of isolated CDH. Using high\u2010density genotyping, seven patients were analyzed by homozygosity exclusion rare allele mapping (HERAM) and phased haplotype sharing (HapShare), two methods we developed to map shared chromosome regions. Our patient cohort shared three regions not previously associated with CDH, that is, 2q11.2\u2013q12.1, 4p13 and 7q11.2, and two regions previously involved in CDH, that is, 8p23.1 and 15q26.2. The latter regions contain <jats:italic>GATA4<\/jats:italic> and <jats:italic>NR2F2<\/jats:italic>, two genes implicated in diaphragm formation in mice. Interestingly, three patients shared the 8p23.1 locus and one of them also harbored the 15q26.2 segment. No coding variants were identified in <jats:italic>GATA4<\/jats:italic> or <jats:italic>NR2F2<\/jats:italic>, but a rare shared variant was found in intron 1 of <jats:italic>GATA4<\/jats:italic>. This work shows the role of heritability in isolated CDH. Our family\u2010based strategy uncovers new chromosomal regions possibly associated with disease, and suggests that non\u2010coding variants of <jats:italic>GATA4<\/jats:italic> and <jats:italic>NR2F2<\/jats:italic> may contribute to the development of isolated CDH. This approach could speed up the discovery of the genes and regulatory elements causing multifactorial diseases, such as isolated CDH. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35664","type":"journal-article","created":{"date-parts":[[2012,11,19]],"date-time":"2012-11-19T21:11:20Z","timestamp":1353359480000},"page":"3137-3147","source":"Crossref","is-referenced-by-count":28,"title":["A family\u2010based paradigm to identify candidate chromosomal regions for isolated congenital diaphragmatic hernia"],"prefix":"10.1002","volume":"158A","author":[{"given":"Cammon B.","family":"Arrington","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B.","family":"Bleyl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nori","family":"Matsunami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil E.","family":"Bowles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami I.","family":"Leppert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley L.","family":"Demarest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Osborne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley A.","family":"Yoder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice L.","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Schiffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald M.","family":"Null","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"DiGeronimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rollins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Faix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Comstock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola J.","family":"Camp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark F.","family":"Leppert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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