5. Conclusion and Future Prospects
Desmin mutations have pleotropic effects and often exhibit incomplete penetrance, but modifier genes that explain this behavior had not been identified. In this study, we show epistatic interaction betweenDES and PDE4DIP mutations. In addition, we find increased mutation burden of the PDE4DIP gene in kindreds with slow AF. The described mutations in this gene impaired the spatially regulated cAMP dependent PKA activation and altered phosphorylation of several proteins that play important roles in cardiac contractile function and conduction. In summary, our study has implicated PDE4DIP in maintenance of cardiac function and as a potential target for development of novel drugs for treatment of arrhythmias and cardiomyopathies.