Generation of human induced pluripotent stem cell (hiPSC) lines (UKMi009-A and UKMi011-A) harboring a homozygous and heterozygous HCN4 variant from a family with inherited sinus node dysfunction (SND).

HCN4, as the predominant pacemaker current (If) in mammalian hearts, encodes the potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 driving spontaneous cardiac rhythmicity. Particularly expressed in sinoatrial cells, If channels are main heart rate regulators. Here, we generated two hiPSC lines from a consanguineous family with SND where the HCN4 variant was either present in heterozygous or homozygous state. Generated hiPSCs enable further cardiomyocyte cell differentiation to provide unique patient-derived SND in-vitro disease models in a gene-dose dependent manner. Both cell lines exhibited normal karyotype, cell morphology, hiPSC marker expression, and differentiation into all three germ layers, confirmed by immunofluorescence staining.