The International Calmodulinopathy Registry: recording the diverse phenotypic spectrum of un-CALM hearts

Mette Nyegaard¹* and Michael T. Overgaard²

¹Department of Biomedicine, Aarhus University, Aarhus, Denmark; and ²Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark

* Corresponding author. Department of Biomedicine, Aarhus University, Høegh-Guldbergsgade 10, Building 1116, DK-8000 Aarhus C, Denmark. Tel: +45 22313602, Email: [email protected]

Take home figure Position and main mechanism of arrhythmogenic calmodulin mutations. (A) Upper: three-dimensional structure of calmodulin in calcium-bound form with mutated residues shown in stick representation (PDB-ID: 1CLL). Lower: individual founder mutations shown on the protein encoded from the representative CALM gene. SUD, sudden unexpected death. (B) Schematic illustration of a cardiomyocyte and the main molecular mechanism for LQTS, CPVT, and mixed phenotypes, indicating main targets (RyR2 in green, CaV1.2 in blue) and correlation with impact on calmodulin C-terminal domain calcium affinity loss. Yellow spheres, calcium ions; CaM, calmodulin.