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De novo frameshift mutation in COUP‐TFII ( NR2F2 ) in human congenital diaphragmatic hernia
Author(s) -
High Frances A.,
Bhayani Pooja,
Wilson Jay M.,
Bult Carol J.,
Donahoe Patricia K.,
Longoni Mauro
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37830
Subject(s) - frameshift mutation , congenital diaphragmatic hernia , diaphragmatic hernia , diaphragmatic breathing , mutation , phenotype , genetics , biology , coding region , medicine , gene , pathology , hernia , surgery , pregnancy , fetus , alternative medicine
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.