TBX5 and Holt-Oram syndrome: Mutations in these genes can cause CHDs; for example, TBX5 mutations are observed in Holt-Oram syndrome, resulting in atrial septal defect (ASD)/VSD, along with limb defects; NOTCH1 mutations are associated with AV septal defects and bicuspid aortic valve, and CRELD1 mutations have been linked to AV canal defects [2,18,37-40].