HCN4 and Sinus bradycardia: Impaired cardiac pacemaker function may be due to reduced impulse formation in the sinoatrial node (SAN), defects in impulse conduction from SAN to atria, or widespread atrial electrophysiological abnormalities [49,50,51,52], but in the present study, we limited ourselves to familial sinus bradycardia due to loss-of-function mutations in HCN4.