TBX5 and Holt-Oram syndrome: Interestingly, increased leucine levels did not cause developmental defects of the limbs, although TBX5 mutations were first identified in patients with Holt–Oram syndrome, which is characterized by limb and cardiac malformation.[50, 51] Contrarily, K‐Leu caused developmental defects in model mice that were different from the TBX5 mutation‐induced CHD phenotypes in humans.