Fig. 4.

Two possible genetic etiologies of CHD. a Monogenic mutations in a key cardiac regulator may be the cause of CHD. A pathogenic E1148 K variant of ZFPM2 in patient B430 decreased the binding of ZFPM2 and GATA4 and attenuated the transcriptional activation of GATA4 on the promoter of ANF. b The majority of the variants in the GATA family member genes and JAG1 occurred sporadically in the patients. However, patients B294 and B393 carried two variants in two genes. B393 carried one variant in JAG1 and one variant in GATA6 variant, shown in a blue color, and B294 carried one variant in JAG1 and one variant in GATA5, shown in a green color. The results support the notion that rare, moderate-effect gene variants occur simultaneously in patients and may increase the susceptibility to cardiac malformations. The interaction between NOTCH signaling and the GATA family members is indispensable for cardiac development