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The objective of this work was to study a type 2 long QT syndrome (LQTS2)-associated mutation (c.1600C\u2009&gt;\u2009T in KCNH2, p.R534C in hERG) in CM-iPSC. Peripheral blood mononuclear cells were isolated from two patients with the R534C mutation and iPSCs were generated. In addition, the same mutation was inserted in a control iPSC line by genome editing using CRISPR\/Cas9. Cells expressed pluripotency markers and showed spontaneous differentiation into the three embryonic germ layers. Electrophysiology demonstrated that action potential duration (APD) of LQTS2 CM-iPSC was significantly longer than that of the control line, as well as the triangulation of the action potentials (AP), implying a longer duration of phase 3. Treatment with the I<jats:sub>Kr<\/jats:sub> inhibitor E4031 only caused APD prolongation in the control line. Patch clamp showed a reduction of I<jats:sub>Kr<\/jats:sub> on LQTS2 CM-iPSC compared to control, but channel activation was not significantly affected. Immunofluorescence for hERG demonstrated perinuclear staining in LQTS2 CM-iPSC. In conclusion, CM-iPSC recapitulated the LQTS2 phenotype and our findings suggest that the R534C mutation in KCNH2 leads to a channel trafficking defect to the plasma membrane.<\/jats:p>","DOI":"10.1038\/s41598-019-55837-w","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T11:03:32Z","timestamp":1576494212000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["R534C mutation in hERG causes a trafficking defect in iPSC-derived cardiomyocytes from patients with type 2 long QT syndrome"],"prefix":"10.1038","volume":"9","author":[{"given":"Fernanda C. 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