{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T21:19:41Z","timestamp":1793481581684,"version":"4.5.0"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T00:00:00Z","timestamp":1560211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013286","name":"Specialized Research Fund for the Doctoral Program of Higher Education of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013286","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Stem Cell Research"],"published-print":{"date-parts":[[2019,7]]},"DOI":"10.1016\/j.scr.2019.101483","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T13:52:57Z","timestamp":1560261177000},"page":"101483","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Pathogenic mechanism and gene correction for LQTS-causing double mutations in KCNQ1 using a pluripotent stem cell model"],"prefix":"10.1016","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-6260","authenticated-orcid":false,"given":"Zhen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lipeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfeng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2331-4761","authenticated-orcid":false,"given":"Qing","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuilan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.scr.2019.101483_bb0005","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1038\/emboj.2013.240","article-title":"Isogenic human pluripotent stem cell pairs reveal the role of a KCNH2 mutation in long-QT syndrome","volume":"32","author":"Bellin","year":"2013","journal-title":"EMBO J."},{"key":"10.1016\/j.scr.2019.101483_bb0010","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/nmeth.2999","article-title":"Chemically defined generation of human cardiomyocytes","volume":"11","author":"Burridge","year":"2014","journal-title":"Nat. Methods"},{"key":"10.1016\/j.scr.2019.101483_bb0015","doi-asserted-by":"crossref","first-page":"11227","DOI":"10.1074\/jbc.M109.086389","article-title":"Generation of human induced pluripotent stem cells from umbilical cord matrix and amniotic membrane mesenchymal cells","volume":"285","author":"Cai","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.scr.2019.101483_bb0020","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1073\/pnas.1523918113","article-title":"A mouse model for adult cardiac-specific gene deletion with CRISPR\/Cas9","volume":"113","author":"Carroll","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.scr.2019.101483_bb0025","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.scr.2019.101483_bb0030","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1161\/CIRCULATIONAHA.109.879643","article-title":"NOS1AP is a genetic modifier of the long-QT syndrome","volume":"120","author":"Crotti","year":"2009","journal-title":"Circulation"},{"key":"10.1016\/j.scr.2019.101483_bb0035","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.hrthm.2013.10.005","article-title":"Single nucleotide polymorphisms in arrhythmia genes modify the risk of cardiac events and sudden death in long QT syndrome","volume":"11","author":"Earle","year":"2014","journal-title":"Heart Rhythm."},{"key":"10.1016\/j.scr.2019.101483_bb0040","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0083005","article-title":"The disease-specific phenotype in cardiomyocytes derived from induced pluripotent stem cells of two long QT syndrome type 3 patients","volume":"8","author":"Fatima","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.scr.2019.101483_bb0045","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4103\/0975-3583.95357","article-title":"Genotype-phenotype analysis of three Chinese families with Jervell and Lange-Nielsen syndrome","volume":"3","author":"Gao","year":"2012","journal-title":"J Cardiovasc Dis Res"},{"issue":"1","key":"10.1016\/j.scr.2019.101483_bb0050","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jacc.2018.04.041","article-title":"Genome editing of induced pluripotent stem cells to decipher cardiac Channelopathy variant","volume":"72","author":"Garg","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.scr.2019.101483_bb0055","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.yjmcc.2008.01.002","article-title":"A splice site mutation in hERG leads to cryptic splicing in human long QT syndrome","volume":"44","author":"Gong","year":"2008","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.scr.2019.101483_bb0060","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jjcc.2013.11.014","article-title":"Novel KCNQ1 splicing mutation in patients with forme fruste LQT1 aggravated by hypokalemia","volume":"64","author":"Imai","year":"2014","journal-title":"J. Cardiol."},{"key":"10.1016\/j.scr.2019.101483_bb0065","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nature09747","article-title":"Modelling the long QT syndrome with induced pluripotent stem cells","volume":"471","author":"Itzhaki","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.scr.2019.101483_bb0070","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nbt.2508","article-title":"RNA-guided editing of bacterial genomes using CRISPR-Cas systems","volume":"31","author":"Jiang","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.scr.2019.101483_bb0075","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/gt.2016.41","article-title":"Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study","volume":"23","author":"Kaminski","year":"2016","journal-title":"Gene Ther."},{"key":"10.1016\/j.scr.2019.101483_bb0080","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1136\/jmedgenet-2016-104153","article-title":"KCNQ1 p.L353L affects splicing and modifies the phenotype in a founder population with long QT syndrome type 1","volume":"54","author":"Kapplinger","year":"2017","journal-title":"J. Med. Genet."},{"key":"10.1016\/j.scr.2019.101483_bb0085","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.scr.2018.07.016","article-title":"Generation of patient-specific induced pluripotent stem cell lines from one patient with Jervell and Lange-Nielsen syndrome, one with type 1 long QT syndrome and two healthy relatives","volume":"31","author":"Kasai-Brunswick","year":"2018","journal-title":"Stem Cell Res."},{"key":"10.1016\/j.scr.2019.101483_bb0090","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1242\/dmm.008409","article-title":"Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture","volume":"5","author":"Lahti","year":"2012","journal-title":"Dis. Model. Mech."},{"key":"10.1016\/j.scr.2019.101483_bb0095","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ijcard.2016.06.081","article-title":"Novel long QT syndrome-associated missense mutation, L762F, in CACNA1C-encoded L-type calcium channel imparts a slower inactivation tau and increased sustained and window current","volume":"220","author":"Landstrom","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"10.1016\/j.scr.2019.101483_bb0100","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/xen.12131","article-title":"Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selection","volume":"22","author":"Li","year":"2015","journal-title":"Xenotransplantation"},{"key":"10.1016\/j.scr.2019.101483_bb0105","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nprot.2012.150","article-title":"Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt\/\u03b2-catenin signaling under fully defined conditions","volume":"8","author":"Lian","year":"2013","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.scr.2019.101483_bb0110","doi-asserted-by":"crossref","first-page":"H2006","DOI":"10.1152\/ajpheart.00694.2011","article-title":"High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents","volume":"301","author":"Ma","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.scr.2019.101483_bb0115","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13287-015-0027-z","article-title":"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","volume":"6","author":"Ma","year":"2015","journal-title":"Stem Cell Res Ther"},{"key":"10.1016\/j.scr.2019.101483_bb0120","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1161\/CIRCULATIONAHA.117.032273","article-title":"Determining the pathogenicity of a genomic variant of uncertain significance using CRISPR\/Cas9 and human-induced pluripotent stem cells","volume":"138","author":"Ma","year":"2018","journal-title":"Circulation"},{"key":"10.1016\/j.scr.2019.101483_bb0125","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1093\/eurheartj\/ehr073","article-title":"Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation","volume":"32","author":"Matsa","year":"2011","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.scr.2019.101483_bb0130","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMoa0908679","article-title":"Patient-specific induced pluripotent stem-cell models for long-QT syndrome","volume":"363","author":"Moretti","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.scr.2019.101483_bb0135","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nbt.2527","article-title":"RNA guides genome engineering","volume":"31","author":"Mussolino","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.scr.2019.101483_bb0140","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1126\/science.aad5143","article-title":"In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy","volume":"351","author":"Nelson","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.scr.2019.101483_bb0145","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1126\/science.aan4187","article-title":"Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9","volume":"357","author":"Niu","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.scr.2019.101483_bb0150","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nature17664","article-title":"Efficient introduction of specific homozygous and heterozygous mutations using CRISPR\/Cas9","volume":"533","author":"Paquet","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.scr.2019.101483_bb0155","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.hrthm.2013.05.014","article-title":"HRS\/EHRA\/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in may 2013 and by ACCF, AHA, PACES, and AEPC in June 2013","volume":"10","author":"Priori","year":"2013","journal-title":"Heart Rhythm."},{"key":"10.1016\/j.scr.2019.101483_bb0160","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1056\/NEJM200007273430405","article-title":"A molecular link between the sudden infant death syndrome and the long-QT syndrome","volume":"343","author":"Schwartz","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.scr.2019.101483_bb0165","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1161\/CIRCULATIONAHA.105.592899","article-title":"The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome","volume":"113","author":"Schwartz","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.scr.2019.101483_bb0170","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.scr.2019.101483_bb0175","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.yjmcc.2006.12.015","article-title":"Mechanistic basis for the pathogenesis of long QT syndrome associated with a common splicing mutation in KCNQ1 gene","volume":"42","author":"Tsuji","year":"2007","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.scr.2019.101483_bb0180","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.hrthm.2018.05.028","article-title":"Complex aberrant splicing in the induced pluripotent stem cell-derived cardiomyocytes from a patient with long QT syndrome carrying KCNQ1-A344Aspl mutation","volume":"15","author":"Wuriyanghai","year":"2018","journal-title":"Heart Rhythm."},{"key":"10.1016\/j.scr.2019.101483_bb0185","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1126\/science.1172482","article-title":"Human induced pluripotent stem cells free of vector and transgene sequences","volume":"324","author":"Yu","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.scr.2019.101483_bb0190","doi-asserted-by":"crossref","first-page":"11866","DOI":"10.1073\/pnas.1205266109","article-title":"Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel","volume":"109","author":"Zhang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.scr.2019.101483_bb0195","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1038\/nprot.2012.115","article-title":"Generation of human induced pluripotent stem cells from urine samples","volume":"7","author":"Zhou","year":"2012","journal-title":"Nat. Protoc."}],"updated-by":[{"DOI":"10.1016\/j.scr.2019.101526","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000}}],"container-title":["Stem Cell Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1873506119301138?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1873506119301138?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T11:31:13Z","timestamp":1761737473000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1873506119301138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7]]},"references-count":39,"alternative-id":["S1873506119301138"],"URL":"https:\/\/doi.org\/10.1016\/j.scr.2019.101483","relation":{},"ISSN":["1873-5061"],"issn-type":[{"value":"1873-5061","type":"print"}],"subject":[],"published":{"date-parts":[[2019,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pathogenic mechanism and gene correction for LQTS-causing double mutations in KCNQ1 using a pluripotent stem cell model","name":"articletitle","label":"Article Title"},{"value":"Stem Cell Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.scr.2019.101483","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"101483"}}