{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:14:17Z","timestamp":1785363257080,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2016A030313279"],"award-info":[{"award-number":["2016A030313279"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Noninvasive Electrocardiol"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Long QT syndrome (LQTS) is a life\u2010threatening inherited channelopathy, and prolonged QT intervals easily trigger malignant arrhythmias, especially torsades de pointes and ventricular fibrillation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>The proband with overlapped phenotypes of LQTS and sinoatrial node dysfunction underwent some necessary examinations, including echocardiography, electrocardiogram (ECG), and Holter monitoring. Next, whole\u2010exome sequencing was performed, and candidate genes were validated by Sanger sequencing. RNA secondary structure and protein physical\u2010chemical parameter analyses were used to predict the possible structural change of the proteins induced by the mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified the digenic heterozygous mutations of KCNH2 p.307_308del (NM_001204798, c.921_923del) and SCN5A p.R1865H (NM_001160160, c.G5594A) in the female and young proband (II: 1) of LQTS and ventricular fibrillation with repeat syncope at rest. Subsequently, she occurred with obvious sinus arrest with persistent ventricular pacing of implantable cardioverter\u2010defibrillator. The heterozygous SCN5Ap.R1865H was carried by her father and sister but not carried by I:2. II:1 carried with KCNH2 p.307_308del as a de novo mutation, but not existed in other family members. RNA secondary structure of KCNH2 p.307_308del showed a false regional double helix, and its amino acids' hydrophobicity was significantly weakened. For the Na<jats:sub>v<\/jats:sub>1.5 protein property, SCN5A p.R1865H slightly increased the molecular weight and aliphatic index but reduced the instability index.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The digenic heterozygous KCNH2 and SCN5A mutations were associated with young early\u2010onset long QT syndrome and sinoatrial node dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/anec.12889","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T10:50:05Z","timestamp":1636541405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Digenic heterozygous mutations of KCNH2 and SCN5A induced young and early\u2010onset long QT syndrome and sinoatrial node dysfunction"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1925-2801","authenticated-orcid":false,"given":"Zhe","family":"Yang","sequence":"first","affiliation":[{"name":"The Cardiovascular Center Department of Cardiology Interventional Medical Center Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat\u2010sen University Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Ma","sequence":"additional","affiliation":[{"name":"The Cardiovascular Center Department of Cardiology Interventional Medical Center Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat\u2010sen University Zhuhai China"},{"name":"BGI Education Center University of Chinese Academy of Sciences Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiana","family":"Huang","sequence":"additional","affiliation":[{"name":"Reproductive Center The Six Affiliated Hospital Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Xian","sequence":"additional","affiliation":[{"name":"The Cardiovascular Center Department of Cardiology Interventional Medical Center Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat\u2010sen University Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Huang","sequence":"additional","affiliation":[{"name":"The Cardiovascular Center Department of Cardiology Interventional Medical Center Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat\u2010sen University Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linbo","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine Jinan University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WenLiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Medicine Jinan University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangdong Cardiovascular Institute Guangdong Geriatrics Institute Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Diseases Chinese 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