Abstract 18021: Combining Human Induced Pluripotent Stem Cell Derived Cardiac Sheets, CRISPR-Based Genome Editing, and Optical Mapping of Rotors to Study the Short QT Syndrome

Introduction: The congenital Short QT Syndrome (SQTS) is a familial arrhythmogenic syndrome caused by abnormal ion channel function leading to action-potential duration (APD) shortening, life-threatening arrhythmias and sudden cardiac death. Aims: 1) To establish a patient-specific two-dimensional (2D) human induced pluripotent stem cell-derived cardiac sheet (hiPSC-CS) disease model of the congenital SQTS. 2) To establish an isogenic control line using gene-editing technology. 3) To characterize the electrical properties of the generated patient-specific hiPSC-CSs at baseline and following drug interventions. Results: Patient-specific hiPSC lines were established from a healthy individual and a symptomatic SQTS patient carrying a missense mutation (N588K) in the hERG gene, leading to gain of function in the rapidly activating delayed rectifier potassium current (IKr). A corrected-SQTS-hiPSC line was established using CRISPR-Cas9 system. All hiPSC lines were directly differentiated into hiPSC-derived card...