ArticleThe EMBO journal2013
Isogenic human pluripotent stem cell pairs reveal the role of a KCNH2 mutation in long-QT syndrome.
Article in The EMBO journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.
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126 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.
- Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes-a systematic review.Pflugers Archiv : European journal of physiology · 2019Pooled it
- Innervated human cardiac muscle model reveals sympathetic drivers of KCNH2-associated arrhythmias.Nature communications · 2026Article
- Article
- Long QT Syndrome Type 5 With Coexisting KCNE1 and RYR2 Variants: A Diagnostic Ambiguity.Clinical case reports · 2026Article
- In vitro modeling of renal injury-induced cardiac effects using human iPSC-derived organoids.Cell communication and signaling : CCS · 2026Article
- Gene Therapy for Inherited Cardiac Arrhythmias.Journal of cardiovascular translational research · 2025Review
- Transformative Potential of Induced Pluripotent Stem Cells in Congenital Heart Disease Research and Treatment.Children (Basel, Switzerland) · 2025Review
- Primary diagnosis of atrioventricular pseudo-block in a neonate with definitive diagnosis of long QT syndrome: diagnostic considerations and therapeutic approaches.International journal of emergency medicine · 2025Article
- Guidelines for managing and using the digital phenotypes of pluripotent stem cell lines.Stem cell reports · 2024Review
- From genes to clinical management: A comprehensive review of long QT syndrome pathogenesis and treatment.Heart rhythm O2 · 2024Review
- Using induced pluripotent stem cells for drug discovery in arrhythmias.Expert opinion on drug discovery · 2024Review
- The electrophysiologic effects of KCNQ1 extend beyond expression of IKs: evidence from genetic and pharmacologic block.Cardiovascular research · 2024Article
- Stem cell models of inherited arrhythmias.Nature cardiovascular research · 2024Review
- Characterizing induced pluripotent stem cells and derived cardiomyocytes: insights from nano scale mass measurements and mechanical properties.Nanoscale advances · 2024Article
- Modeling mutation-specific arrhythmogenic phenotypes in isogenic human iPSC-derived cardiac tissues.Scientific reports · 2024Article
- Evaluating pro-arrhythmogenic effects of the T634S-hERG mutation: insights from a simulation study.Interface focus · 2023Article
- Heart and kidney organoids maintain organ-specific function in a microfluidic system.Materials today. Bio · 2023Article
- The Role of Genetics in the Management of Heart Failure Patients.International journal of molecular sciences · 2023Review
- Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models.Genes · 2023Review
- Single-Cell Analysis of Contractile Forces in iPSC-Derived Cardiomyocytes: Paving the Way for Precision Medicine in Cardiovascular Disease.International journal of molecular sciences · 2023Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patient-specific induced pluripotent stem cells (iPSCs) will assist research on genetic cardiac maladies if the disease phenotype is recapitulated in vitro. However, genetic background variations may confound disease traits, especially for disorders with incomplete penetrance, such as long-QT syndromes (LQTS). To study the LQT2-associated c.A2987T (N996I) KCNH2 mutation under genetically defined conditions, we derived iPSCs from a patient carrying this mutation and corrected it. Furthermore, we introduced the same point mutation in human embryonic stem cells (hESCs), generating two genetically distinct isogenic pairs of LQTS and control lines. Correction of the mutation normalized the current (IKr) conducted by the HERG channel and the action potential (AP) duration in iPSC-derived cardiomyocytes (CMs). Introduction of the same mutation reduced IKr and prolonged the AP duration in hESC-derived CMs. Further characterization of N996I-HERG pathogenesis revealed a trafficking defect. Our results demonstrated that the c.A2987T KCNH2 mutation is the primary cause of the LQTS phenotype. Precise genetic modification of pluripotent stem cells provided a physiologically and functionally relevant human cellular context to reveal the pathogenic mechanism underlying this specific disease phenotype.
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