NKX2-5 and ventricular septal defect: Genetic studies in humans have associated Nkx2-5 coding region point mutations with the familial and sporadic occurrence of congenital heart anomalies such as tetralogy of Fallot (ToF), ventricular septal defect (VSD), and atrial septal defect (ASD) similar to those observed in mouse knockout or hypomorphic expression mutants1–6.