Identification of PITX2 as a novel factor in arrhythmogenic cardiomyopathy pathogenesis [patient line]
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ABSTRACT: In this study, we identified a novel heterozygous variant within DSP (c.3562T>C) in a patient diagnosed with ACM. Using CRISPR/Cas9 we corrected patient-derived human induced pluripotent stem cells (hiPSC) and created a knock-in (KI) hiPSC line with the same mutation. Compared to wildtype cardiomyocytes, we observed a prolonged action potential duration (APD) and reduced expression of desmosomal components, which was paralleled by abnormal levels of essential cardiac ion channels. Strikingly, the transcription factor paired-like homeodomain 2 (PITX2), which acts as a repressor of ion channel-related genes, was induced in these cells. Together, we identified PITX2 as a potential missing link between mutations in DSP and the cardiac conductance abnormalities often seen in these patients.
ORGANISM(S): Homo sapiens
PROVIDER: GSE208213 | GEO | 2023/03/02
REPOSITORIES: GEO
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