This study firstly associates MEF2C loss-of-function mutation with DORV in humans, which provides novel insight into the molecular pathogenesis of CHD, suggesting potential implications for genetic counseling and personalized treatment of CHD patients.
Furthermore, the mutation significantly diminished the synergistic activation between MEF2C and GATA4, another cardiac core transcription factor that has been causally linked to CHD.
Our results provide the first demonstration of MEF2C mutation and suggest that disturbances in the regulatory circuits involving these cardiac transcription factors may cause a subset of non-syndromic and non-familial CHDs.