{"id":6537,"date":"2023-02-17T06:49:22","date_gmt":"2023-02-17T06:49:22","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2021-overlap-arrhythmia-syndromes-resulting-from-multiple-genetic-variations-studied-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes\/"},"modified":"2023-02-17T06:49:23","modified_gmt":"2023-02-17T06:49:23","slug":"2021-overlap-arrhythmia-syndromes-resulting-from-multiple-genetic-variations-studied-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2021-overlap-arrhythmia-syndromes-resulting-from-multiple-genetic-variations-studied-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes\/","title":{"rendered":"2021 &#8211; Overlap Arrhythmia Syndromes Resulting from Multiple Genetic Variations Studied in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes"},"content":{"rendered":"<p>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are used\u00a0for genetic models of cardiac diseases. We report an arrhythmia syndrome consisting of Early\u00a0Repolarization Syndrome (ERS) and Short QT Syndrome (SQTS). The index patient (MMRL1215)\u00a0developed arrhythmia-mediated syncope after electrocution and was found to carry six mutations.\u00a0Functional alterations resulting from these mutations were examined in patient-derived hiPSC-CMs.\u00a0Electrophysiological recordings were made in hiPSC-CMs from MMRL1215 and healthy controls.\u00a0ECG analysis of the index patient showed slurring of the QRS complex and QTc = 326 ms. Action\u00a0potential (AP) recordings from MMRL1215 myocytes showed slower spontaneous activity and AP\u00a0duration was shorter. Field potential recordings from MMRL1215 hiPSC-CMs lack a \u201cpseudo\u201d QRS\u00a0complex suggesting reduced inward current(s). Voltage clamp analysis of ICa\u00a0showed no difference in\u00a0the magnitude of current. Measurements of INa\u00a0reveal a 60% reduction in INa\u00a0density in MMRL1215\u00a0hiPSC-CMs. Steady inactivation and recovery of INa\u00a0was unaffected. mRNA analysis revealed\u00a0ANK2 and SCN5A are significantly reduced in hiPSC-CM derived from MMRL1215, consistent with\u00a0electrophysiological recordings. The polygenic cause of ERS\/SQTS phenotype is likely due to a loss\u00a0of INa\u00a0due to a mutation in\u00a0PKP2\u00a0coupled with and a gain of function in IK,ATP\u00a0due to a mutation\u00a0in\u00a0ABCC9.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[34],"resource_type":[75],"application_areas":[77],"therapeutic_areas":[54],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-6537","resource_library","type-resource_library","status-publish","hentry","products_tags-cardioexcyte-96","resource_type-publication","application_areas-cell-ipscs-profiling","therapeutic_areas-cardiac-safety-cipa"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6537","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6537"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6537"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6537"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6537"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6537"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6537"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6537"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6537"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6537"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}