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Type 1 long QT syndrome (LQT1) is a common type of cardiac channelopathy associated with loss-of-function mutations of  KCNQ1 . Currently there is a lack of drugs that target the defected slowly activating delayed rectifier potassium channel (IKs) .  With LQT1 patient-specific human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs), we tested the effects of a selective IKs activator ML277 on reversing the disease phenotypes.    Methods  A LQT1 family with a novel heterozygous exon 7 deletion in the  KCNQ1  gene was identified. Dermal fibroblasts from the proband and her healthy father were reprogrammed to hiPSCs and subsequently differentiated into hiPSC-CMs.    Results  Compared with the control, LQT1 patient hiPSC-CMs showed reduced levels of wild type  KCNQ1  mRNA accompanied by multiple exon skipping mRNAs and a ~50% reduction of the full length Kv7.1 protein. Patient hiPSC-CMs showed reduced IKs current (tail current density at 30 mV: 0.33 ± 0.02 vs. 0.92 ± 0.21, P < 0.05) and prolonged action potential duration (APD) (APD 50 and APD90: 603.9 ± 39.2 vs. 319.3 ± 13.8 ms, P < 0.005; and 671.0 ± 41.1 vs. 372.9 ± 14.2 ms, P < 0.005). ML277, a small molecule recently identified to selectively activate K V 7.1, reversed the decreased IKs and partially restored APDs in patient hiPSC-CMs.    Conclusions  From a LQT1 patient carrying a novel heterozygous exon7 deletion mutation of  KCNQ1 , we generated hiPSC-CMs that faithfully recapitulated the LQT1 phenotypes that are likely associated with haploinsufficiency and trafficking defect of  KCNQ1 /Kv7.1. The small molecule ML277 restored IKs function in hiPSC-CMs and could have therapeutic value for LQT1 patients.    Electronic supplementary material  The online version of this article (doi:10.1186/s13287-015-0027-z) contains supplementary material, which is available to authorized users.

stem cell research and therapy

Characterization of a novel KCNQ1 mutation for type 1 long QT syndrome and assessment of the therapeutic potential of a novel IKs activator using patient-specific induced pluripotent stem cell-derived cardiomyocytes