Identification of dosage‐sensitive genes in fetuses referred with severe isolated congenital diaphragmatic hernia. (14th November 2013)

• Record Type: Journal Article
• Authors: Brady, P. D.; DeKoninck, P.; Fryns, J. P.; Devriendt, K.; Deprest, J. A.; Vermeesch, J. R.
• Is Part Of: Prenatal diagnosis. Volume 33:Number 13(2013:Dec.)
• Page Start: 1283
• Page End: 1292
• Publication Date: 2013-11-14
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.4244
• Languages: English
• ISSNs: 0197-3851

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="pd4244-sec-0001" sec-type="section"> <title>Objective</title> <p>Congenital diaphragmatic hernia (CDH) is a fetal abnormality affecting diaphragm and lung development with a high mortality rate despite advances in fetal and neonatal therapy. CDH may occur either as an isolated defect or in syndromic form for which the prognosis is worse. Although conventional karyotyping and, more recently, chromosomal microarrays support a substantial role for genetic factors, causal genes responsible for isolated CDH remain elusive. We propose that chromosomal microarray analysis will identify copy number variations (CNVs) associated with isolated CDH.</p> </sec> <sec id="pd4244-sec-0002" sec-type="section"> <title>Methods</title> <p>We perform a prospective genome‐wide screen for CNVs using chromosomal microarrays on 75 fetuses referred with apparently isolated CDH, six of which were later reclassified as non‐isolated CDH.</p> </sec> <sec id="pd4244-sec-0003" sec-type="section"> <title>Results</title> <p>The results pinpoint haploinsufficiency of <italic>NR2F2</italic> as a cause of CDH and cardiovascular malformations. In addition, the 15q25.2 and 16p11.2 recurrent microdeletions are associated with isolated CDH. By using gene prioritisation and network analysis, we provide strong evidence for several novel dosage‐sensitive candidate genes associated with CDH.</p> </sec> <sec id="pd4244-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Chromosomal microarray analysis detects submicroscopic CNVs associated with isolated CDH or CDH with cardiovascular malformations. © 2013 John Wiley & Sons, Ltd.</p> </sec> </abstract>