Mice deficient for one copy of the Gata4 gene have been described with CDH and heart defects suggesting mutations in Gata4 can cause the phenotype in mice.
In summary, GATA4 is implicated in both familial and sporadic CDH, and our data suggests that WES may be a powerful tool to discover rare variants for CDH.
Our family-based strategy uncovers new chromosomal regions possibly associated with disease, and suggests that non-coding variants of GATA4 and NR2F2 may contribute to the development of isolated CDH.
Inherited deletions of ZFPM2 were identified in 2 patients with isolated diaphragmatic defects and a large de novo 8q deletion overlapping the same gene was found in a patient with non-isolated CDH.
Inherited deletions of ZFPM2 were identified in 2 patients with isolated diaphragmatic defects and a large de novo 8q deletion overlapping the same gene was found in a patient with non-isolated CDH.
The COUP-TFII, FOG2, and GATA4 genes, regulated by the retinoid signaling pathway, are located on chromosomes 15q26, 8q23, and 8p23.1 respectively, regions reported to be deleted in individuals with CDH.
Here we focused on genes from 15q26, the best-characterized CDH-critical region, as well as FOG2 and GATA4, genes singled out from CDH-critical regions at 8q22-8q23 and 8p23.1, respectively.
For FOG2, we identified novel sequence alterations predicting p.M703L and p.T843A in two patients with isolated CDH that were absent in 526 and 564 control chromosomes respectively.
The expression of the WT1 gene in pleural and abdominal mesothelium and the occurrence of diaphragmatic hernia in transgenic mice with a homozygous WT1 deletion strongly suggests that the diaphragmatic hernia in this patient is part of the malformation pattern caused by WT1 mutations.