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Gain\u2010of\u2010function mutations in the cardiac ryanodine receptor gene (<jats:italic>RYR2<\/jats:italic>) account for the majority of CPVT cases, causing substantial disruption of intracellular calcium (Ca<jats:sup>2+<\/jats:sup>) homeostasis particularly during the periods of \u03b2\u2010adrenergic receptor stimulation. However, the highly variable penetrance, patient outcomes, and drug responses observed in clinical practice remain unexplained, even for patients with well\u2010established founder RyR2 mutations. Therefore, investigation of the electrophysiological consequences of CPVT\u2010causing RyR2 mutations is crucial to better understand the pathophysiology of the disease. The development of strategies for reprogramming human somatic cells to human induced pluripotent stem cells (hiPSCs) has provided a unique opportunity to study inherited arrhythmias, due to the ability of hiPSCs to differentiate down a cardiac lineage. Employment of genome editing enables generation of disease\u2010specific cell lines from healthy and diseased patient\u2010derived hiPSCs, which subsequently can be differentiated into cardiomyocytes. This paper describes the means for establishing an hiPSC\u2010based model of CPVT in order to recapitulate the disease phenotype <jats:italic>in vitro<\/jats:italic> and investigate underlying pathophysiological mechanisms. The framework of this approach has the potential to contribute to disease modeling and personalized medicine using hiPSC\u2010derived cardiomyocytes. \u00a9 2021 Wiley Periodicals LLC.<\/jats:p>","DOI":"10.1002\/cpz1.320","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T19:41:59Z","timestamp":1640634119000},"source":"Crossref","is-referenced-by-count":7,"title":["Using hiPSC\u2010CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia"],"prefix":"10.1002","volume":"1","author":[{"given":"Alia","family":"Arslanova","sequence":"first","affiliation":[{"name":"Cellular and Regenerative Medicine Centre British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"},{"name":"Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanam","family":"Shafaattalab","sequence":"additional","affiliation":[{"name":"Cellular and Regenerative Medicine Centre British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"},{"name":"Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Ye","sequence":"additional","affiliation":[{"name":"Cellular and Regenerative Medicine Centre British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"},{"name":"Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parisa","family":"Asghari","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences, Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Lin","sequence":"additional","affiliation":[{"name":"Cellular and Regenerative Medicine Centre British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"},{"name":"Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"BaRun","family":"Kim","sequence":"additional","affiliation":[{"name":"Molecular Cardiac Physiology Group, Departments of Biomedical Physiology and Kinesiology and Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Roston","sequence":"additional","affiliation":[{"name":"British Columbia Children's Hospital Heart Center  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif","family":"Hove\u2010Madsen","sequence":"additional","affiliation":[{"name":"Cardiac Rhythm and Contraction Group, IIBB\u2010CSIC, CIBERCV, IIB Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip","family":"Van Petegem","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shubhayan","family":"Sanatani","sequence":"additional","affiliation":[{"name":"British Columbia Children's Hospital Heart Center  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin","family":"Moore","sequence":"additional","affiliation":[{"name":"Cardiac Rhythm and Contraction Group, IIBB\u2010CSIC, CIBERCV, IIB Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Lynn","sequence":"additional","affiliation":[{"name":"Cellular and Regenerative Medicine Centre British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mads","family":"S\u00f8ndergaard","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonglun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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