We have performed High resolution melting (HRM) mutation scanning of GATA4 coding exons of nonsyndrome 100 patients as a case group including 39 atrial septal defects (ASD), 57 ventricular septal defects (VSD) and four patients with both above defects and 50 healthy individuals as a control group.
Furthermore, the mutation disrupted the synergistic activation between NKX2.5 and GATA binding protein 4, another cardiac core transcription factor associated with ASD.
Our study broadens the mutation spectrum of the GATA4 gene and reveals for the first time a mutation at the methylation position of GATA4 associated with ASD.
Our previous study indicated that 8 patients from a family with a history of congenital heart disease had simple atrial septal defect (ASD) and carried the same mutation at codon 310 in the GATA4 gene.
Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO.
In this study, the entire coding region of GATA4, a gene encoding a zinc-finger transcription factor crucial to embryogenesis, was initially sequenced in 120 unrelated patients with ASD.
Finally, useful information is yet available with regard to genes causing isolated CHDs in individuals who do not have a genetic syndrome (an example is the mutation of NKX2.5 and GATA4 genes causing atrial septal defect).
The cardiac transcription factor GATA4 has not previously been implicated in a human disorder but a recent paper by Garg et al. provides evidence of mutations in GATA4 that cause atrial septal defects.