{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T18:08:23Z","timestamp":1775585303693,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,7,19]],"date-time":"2018-07-19T00:00:00Z","timestamp":1531958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Erasmus+Program of the European Union","award":["2013-0040"],"award-info":[{"award-number":["2013-0040"]}]},{"name":"Belgian Science Policy Office Interuniversity Attraction Poles","award":["IAP P7\/43-BeMGI"],"award-info":[{"award-number":["IAP P7\/43-BeMGI"]}]},{"name":"Herculesfoundation","award":["ZW11-14"],"award-info":[{"award-number":["ZW11-14"]}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital diaphragmatic hernia (CDH) is characterized by a defective closure of the diaphragm occurring as an isolated defect in 60% of cases. Lung size, liver herniation, and pulmonary circulation are major prognostic indices. Isolated CDH genetics is heterogeneous and poorly understood. Whether genetic lesions are also outcome determinants has never been explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To identify isolated CDH genetic causes, to fine map the mutational burden, and to search for a correlation between the genotype and the disease severity and outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Targeted massively parallel sequencing of 143 human and mouse CDH causative and candidate genes in a cohort of 120 fetuses with isolated CDH and detailed outcome measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pathogenic and likely pathogenic variants were identified in 10% of the cohort. These variants affect both known CDH causative genes, namely, <jats:italic>ZFPM2<\/jats:italic>, <jats:italic>GATA4<\/jats:italic>, and <jats:italic>NR2F2<\/jats:italic>, and new genes, namely, <jats:italic>TBX1<\/jats:italic>, <jats:italic>TBX5<\/jats:italic>, <jats:italic>GATA5<\/jats:italic>, and <jats:italic>PBX1<\/jats:italic>. In addition, mutation burden analysis identified <jats:italic>LBR<\/jats:italic>, <jats:italic>CTBP2<\/jats:italic>, <jats:italic>NSD1<\/jats:italic>, <jats:italic>MMP14<\/jats:italic>, <jats:italic>MYOD1<\/jats:italic>, and <jats:italic>EYA1<\/jats:italic> as candidate genes with enrichment in rare but predicted deleterious variants. No obvious correlation between the genotype and the phenotype or short\u2010term outcome has been found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Targeted resequencing identifies a genetic cause in 10% of isolated CDH and identifies new candidate genes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.5327","type":"journal-article","created":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T18:21:00Z","timestamp":1530555660000},"page":"654-663","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted next\u2010generation sequencing"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7488-0694","authenticated-orcid":false,"given":"Molka","family":"Kammoun","sequence":"first","affiliation":[{"name":"Department for Human Genetics Katholieke Universiteit Leuven  Leuven 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Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Gratacos","sequence":"additional","affiliation":[{"name":"Fetal i+D Fetal Medicine Research Center, BCNatal \u2010 Barcelona Center for Maternal\u2010Fetal and Neonatal Medicine (Hospital Cl\u00ednic and Hospital Sant Joan de Deu), Institut Cl\u00ednic de Ginecologia, Obstetricia i Neonatologia, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Universitat de Barcelona  Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koen","family":"Devriendt","sequence":"additional","affiliation":[{"name":"Department for Human Genetics Katholieke Universiteit Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisenda","family":"Eixarch","sequence":"additional","affiliation":[{"name":"Fetal i+D Fetal Medicine Research Center, BCNatal \u2010 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