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.