Novel mutation in N-terminal fragment of ryanodine receptor 2 causing catecholaminergic polymorphic ventricular tachycardia

Fig. 1. (A) 12-lead ECG, (B) A representative episode of ICD treated polymorphic ventricular tachycardia.

Fig. 2. Schematic illustration of RyR2, a large 4967-amino acid sarcoplasmic reticulum protein. ∗: Highlighted is the c.1195A > G (p.Met399Val) variant of RyR2, a novel disease-causing RyR2 variant through its role as a binding site for FKBP12.6/calstabin-2. Known CPVT mutation clusters are shown as dotted lines, with amino acid numbers indicating their boundaries (residues 1–466, 2246–2534, 3778–4201, 4497–4959). Figure adapted from: Blayney LM, Lai FA. Ryanodine receptor-mediated arrhythmias and sudden cardiac death. Pharmacol Ther. 2009; 123(2):151–177. https://doi.org/10.1016/j.pharmthera.2009.03.006.

Fig. 3. Pathophysiology of RyR2 mutation at binding site of FKBP12.6 leading to aberrant opening of the channel in diastole. Figure adapted from: • Wleklinski MJ, Kannankeril PJ, Knollmann BC. Molecular and tissue mechanisms of catecholaminergic polymorphic ventricular tachycardia. J Physiol. 2020; 598(14):2817–2834. https://doi.org/10.1113/JP276757 • Tong M, Jiang Y. FK506-Binding Proteins and Their Diverse Functions. Curr Mol Pharmacol. 2015; 9(1):48–65. https://doi.org/10.2174/1874467208666150519113541.