De novo frameshift mutation in COUP‐TFII (NR2F2) in human congenital diaphragmatic hernia. Issue 9 (1st July 2016)

• Record Type: Journal Article
• Authors: High, Frances A.; Bhayani, Pooja; Wilson, Jay M.; Bult, Carol J.; Donahoe, Patricia K.; Longoni, Mauro
• Is Part Of: American journal of medical genetics. Volume 170:Issue 9(2016)
• Page Start: 2457
• Page End: 2461
• Publication Date: 2016-07-01
• Subjects: COUP‐TFII -- NR2F2 -- 15q26 -- congenital diaphragmatic hernia -- atrial septal defect -- de novo -- trio -- pleuroperitoneal folds; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.37830
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : COUP‐TFII ( NR2F2 ) is mapped to the 15q26 deletion hotspot associated with the common and highly morbid congenital diaphragmatic hernia (CDH). Conditional homozygous deletions of COUP‐TFII in mice result in diaphragmatic defects analogous to the human Bochdalek‐type hernia phenotype. Despite evidence from animal models however, mutations in the coding sequence of COUP‐TFII have not been reported in patients, prompting the speculation that additional coding or non‐coding sequences in the 15q26 locus are necessary for diaphragmatic hernias to develop. In this report, we describe a case of a patient with a heterozygous de novo COUP‐TFII frameshift mutation, presenting with CDH and an atrial septal defect. The p.Pro33Ala fs Ter77 mutation specifically disrupts protein isoform 1 which contains the DNA binding domain. In addition, we review other COUP‐TFII sequence variations and deletions that have been described in cases of CDH. We conclude that COUP‐TFII mutations can cause diaphragmatic hernias, and should be included in the differential diagnosis of CDH patients, particularly those with comorbid congenital heart defects. © 2016 Wiley Periodicals, Inc.