Dysregulated Expression Of Ankyrin Repeat Domain 1 In The Developing Myocardium Causes Anomalous Venous Return And Morphogenetic Defects By Impairing Cardiac Remodelling

Aim: Total anomalous pulmonary venous return (TAPVR) is a severe congenital heart disease characterized by failure of pulmonary veins to connect exclusively to the left atrium. Cardiac Ankyrin Repeat Protein (CARP), encoded by the Ankyrin repeat domain 1 (Ankrd1) gene, is a mechanosensor protein, involved in physiological and pathological remodelling of myocardium. Recently, we have identified Ankrd1 as a candidate gene for TAPVR in isolated patients. Our reported TAPVR patients presented either increased Ankrd1 transcript levels or a missense T116M mutation, resulting in greater protein stability. To date, the role of this gene in venous pole development, as well as the link between an Ankrd1 gain of function condition and TAPVR pathogenesis in humans remain unexplored.