{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:23:45Z","timestamp":1790619825035,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Natural Science Foundation of China","award":["81873487"],"award-info":[{"award-number":["81873487"]}]},{"name":"The National Natural Science Foundation of China","award":["2022D01E22"],"award-info":[{"award-number":["2022D01E22"]}]},{"name":"The National Natural Science Foundation of China","award":["20210215"],"award-info":[{"award-number":["20210215"]}]},{"name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","award":["81873487"],"award-info":[{"award-number":["81873487"]}]},{"name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","award":["2022D01E22"],"award-info":[{"award-number":["2022D01E22"]}]},{"name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","award":["20210215"],"award-info":[{"award-number":["20210215"]}]},{"name":"Hospital Project Fund of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, China","award":["81873487"],"award-info":[{"award-number":["81873487"]}]},{"name":"Hospital Project Fund of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, China","award":["2022D01E22"],"award-info":[{"award-number":["2022D01E22"]}]},{"name":"Hospital Project Fund of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, China","award":["20210215"],"award-info":[{"award-number":["20210215"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Congenital long QT syndrome is a type of inherited cardiovascular disorder characterized by prolonged QT interval. Patient often suffer from syncopal episodes, electrocardiographic abnormalities and life-threatening arrhythmia. Given the complexity of the root cause of the disease, a combination of clinical diagnosis and drug screening using patient-derived cardiomyocytes represents a more effective way to identify potential cures. We identified a long QT syndrome patient carrying a heterozygous KCNQ1 c.656G&gt;A mutation and a heterozygous TRPM4 c.479C&gt;T mutation. Implantation of implantable cardioverter defibrillator in combination with conventional medication demonstrated limited success in ameliorating long-QT-syndrome-related symptoms. Frequent defibrillator discharge also caused deterioration of patient quality of life. Aiming to identify better therapeutic agents and treatment strategy, we established a patient-specific iPSC line carrying the dual mutations and differentiated these patient-specific iPSCs into cardiomyocytes. We discovered that both verapamil and lidocaine substantially shortened the QT interval of the long QT syndrome patient-specific cardiomyocytes. Verapamil treatment was successful in reducing defibrillator discharge frequency of the KCNQ1\/TRPM4 dual mutation patient. These results suggested that verapamil and lidocaine could be alternative therapeutic agents for long QT syndrome patients that do not respond well to conventional treatments. In conclusion, our approach indicated the usefulness of the in vitro disease model based on patient-specific iPSCs in identifying pharmacological mechanisms and drug screening. The long QT patient-specific iPSC line carrying KCNQ1\/TRPM4 dual mutations also represents a tool for further understanding long QT syndrome pathogenesis.<\/jats:p>","DOI":"10.3390\/cells11162495","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T21:15:05Z","timestamp":1660252505000},"page":"2495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In Vitro Drug Screening Using iPSC-Derived Cardiomyocytes of a Long QT-Syndrome Patient Carrying KCNQ1 &amp; TRPM4 Dual Mutation: An Experimental Personalized Treatment"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9822-4285","authenticated-orcid":false,"given":"Feifei","family":"Wang","sequence":"first","affiliation":[{"name":"Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China"},{"name":"Xinjiang Key Laboratory 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Xinjiang Medical University, Urumqi 830000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Xing","sequence":"additional","affiliation":[{"name":"Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China"},{"name":"Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4374-3245","authenticated-orcid":false,"given":"Yankai","family":"Guo","sequence":"additional","affiliation":[{"name":"Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China"},{"name":"Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5220-3972","authenticated-orcid":false,"given":"Jianghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China"},{"name":"Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1532-680X","authenticated-orcid":false,"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China"},{"name":"Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of 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