Link: http://www.ncbi.nlm.nih.gov/pubmed/27363585

Am J Med Genet A. 2016 Jul 1. doi: 10.1002/ajmg.a.37830. [Epub ahead of print]
De novo frameshift mutation in COUP-TFII (NR2F2) in human congenital diaphragmatic hernia.
High FA1,2,3,4, Bhayani P1, Wilson JM3,4, Bult CJ5, Donahoe PK1,3,6, Longoni M1,3.
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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.Pro33AlafsTer77 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.