Additionally, results from human and animal studies illustrated that the mutation of NKX2-5 was not common and usually cause severe congenital heart diseases, including atrial septal defect, double-outlet right ventricle, or Fallot, along with PFO (Biben et al., 2000; Du M et al., 2016; Elliott et al., 2003; 2010). Here, NKX2-5 is linked to Patent foramen ovale.