{"doi":"10.1016/j.ebiom.2020.103024","title":"Modeling polymorphic ventricular tachycardia at rest using patient-specific induced pluripotent stem cell-derived cardiomyocytes","abstract":"BACKGROUND: While mutations in the cardiac type 2 ryanodine receptor (RyR2) have been linked to exercise-induced or catecholaminergic polymorphic ventricular tachycardia (CPVT), its association with polymorphic ventricular tachycardia (PMVT) occurring at rest is unclear. We aimed at constructing a patient-specific human-induced pluripotent stem cell (hiPSC) model of PMVT occurring at rest linked to a single point mutation in RyR2. METHODS: Blood samples were obtained from a patient with PMVT at rest due to a heterozygous RyR2-H29D mutation. Patient-specific hiPSCs were generated from the blood samples, and the hiPSC-derived cardiomyocytes (CMs) were generated via directed differentiation. Using CRIPSR/Cas9 technology, isogenic controls were generated by correcting the RyR2-H29D mutation. Using patch-clamp, fluorescent confocal microscopy and video-image-based analysis, the molecular and functional properties of RyR2-H29D hiPSCCMs and control hiPSCCMs were compared. FINDINGS: release in RyR2-H29D hiPSCCMs. RyR2-H29D hiPSCCMs exhibit shorter action potentials, delayed afterdepolarizations, arrhythmias and aberrant contractile properties compared to isogenic controls. The RyR2-H29D mutation causes post-translational remodeling that is fully reversed with isogenic controls. INTERPRETATION: homeostasis, shortened action potentials, arrhythmias and abnormal contractile properties. FUNDING: French Muscular Dystrophy Association (AFM; project 16,073, MNM2 2012 and 20,225), \"Fondation de la Recherche Médicale\" (FRM; SPF20130526710), \"Institut National pour la Santé et la Recherche Médicale\" (INSERM), National Institutes of Health (ARM; R01 HL145473) and New York State Department of Health (NYSTEM C029156).","journal":"EBioMedicine","year":2020,"id":96715,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":480079,"name":"Monia Souidi","orcid":null,"position":1,"is_corresponding":false},{"id":479097,"name":"Ritu Kumar","orcid":"0000-0002-9995-0078","position":2,"is_corresponding":false},{"id":479098,"name":"Ellen Yang","orcid":"0009-0008-9557-5988","position":3,"is_corresponding":false},{"id":109214,"name":"Fabrice Jaffré","orcid":"0000-0002-4858-1954","position":4,"is_corresponding":false},{"id":291183,"name":"Ting Zhou","orcid":"0000-0003-1423-1507","position":5,"is_corresponding":false},{"id":480080,"name":"Albin Bernardin","orcid":null,"position":6,"is_corresponding":false},{"id":468151,"name":"Steve Reiken","orcid":"0000-0002-5807-3574","position":7,"is_corresponding":false},{"id":479099,"name":"Olivier Cazorla","orcid":"0000-0003-0775-203X","position":8,"is_corresponding":false},{"id":479100,"name":"Andrey V. Kajava","orcid":"0000-0002-2342-6886","position":9,"is_corresponding":false},{"id":479101,"name":"Adrien Moreau","orcid":"0000-0003-3100-0807","position":10,"is_corresponding":false},{"id":479102,"name":"Jean‐Luc Pasquié","orcid":"0000-0003-3773-5804","position":11,"is_corresponding":false},{"id":312237,"name":"Andrew R. Marks","orcid":"0000-0002-4316-5775","position":12,"is_corresponding":false},{"id":479103,"name":"Bruce B. Lerman","orcid":"0000-0001-6780-2903","position":13,"is_corresponding":false},{"id":109234,"name":"Shuibing Chen","orcid":"0000-0002-6294-5187","position":14,"is_corresponding":false},{"id":479104,"name":"Jim W. Cheung","orcid":"0000-0002-4574-9360","position":15,"is_corresponding":false},{"id":109233,"name":"Todd Evans","orcid":"0000-0002-7148-9849","position":16,"is_corresponding":false},{"id":468159,"name":"Alain Lacampagne","orcid":"0000-0003-0264-1787","position":17,"is_corresponding":false},{"id":479105,"name":"Albano C. Méli","orcid":"0000-0002-1727-3027","position":18,"is_corresponding":false},{"id":479096,"name":"Yvonne Sleiman","orcid":"0000-0002-1550-8945","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T22:35:06.014648Z","pmid":"32980690","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}