The D425N mutation of GATA4 has been reported previously in three patients with secundum ASD, VSD, and tetralogy of Fallot.34,35 This variation replaces a negatively charged aspartic acid (D) residue for an uncharged asparagine (N) residue in a position where only negatively charged amino acids are found in GATA4 orthologs in wide range of vertebrate species (Figure 4C). Here, GATA4 is linked to atrial septal defect.