{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:37:58Z","timestamp":1780670278011,"version":"3.54.1"},"reference-count":147,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,10]],"date-time":"2021-04-10T00:00:00Z","timestamp":1618012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science","award":["20K08487"],"award-info":[{"award-number":["20K08487"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Most causal genes for inherited arrhythmia syndromes (IASs) encode cardiac ion channel-related proteins. Genotype-phenotype studies and functional analyses of mutant genes, using heterologous expression systems and animal models, have revealed the pathophysiology of IASs and enabled, in part, the establishment of causal gene-specific precision medicine. Additionally, the utilization of induced pluripotent stem cell (iPSC) technology have provided further insights into the pathophysiology of IASs and novel promising therapeutic strategies, especially in long QT syndrome. It is now known that there are atypical clinical phenotypes of IASs associated with specific mutations that have unique electrophysiological properties, which raises a possibility of mutation-specific precision medicine. In particular, patients with Brugada syndrome harboring an SCN5A R1632C mutation exhibit exercise-induced cardiac events, which may be caused by a marked activity-dependent loss of R1632C-Nav1.5 availability due to a marked delay of recovery from inactivation. This suggests that the use of isoproterenol should be avoided. Conversely, the efficacy of \u03b2-blocker needs to be examined. Patients harboring a KCND3 V392I mutation exhibit both cardiac (early repolarization syndrome and paroxysmal atrial fibrillation) and cerebral (epilepsy) phenotypes, which may be associated with a unique mixed electrophysiological property of V392I-Kv4.3. Since the epileptic phenotype appears to manifest prior to cardiac events in this mutation carrier, identifying KCND3 mutations in patients with epilepsy and providing optimal therapy will help prevent sudden unexpected death in epilepsy. Further studies using the iPSC technology may provide novel insights into the pathophysiology of atypical clinical phenotypes of IASs and the development of mutation-specific precision medicine.<\/jats:p>","DOI":"10.3390\/ijms22083930","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T03:04:06Z","timestamp":1618196646000},"page":"3930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Towards Mutation-Specific Precision Medicine in Atypical Clinical Phenotypes of Inherited Arrhythmia Syndromes"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9635-2769","authenticated-orcid":false,"given":"Tadashi","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuntaro","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Kurabayashi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9611-2303","authenticated-orcid":false,"given":"Yoshiaki","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1007\/s00246-019-02151-x","article-title":"Long QT Syndrome: Genetics and Future Perspective","volume":"40","author":"Wallace","year":"2019","journal-title":"Pediatr. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fcvm.2018.00149","article-title":"Recent Advances in Short QT Syndrome","volume":"5","author":"Campuzano","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_3","first-page":"665","article-title":"J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge","volume":"19","author":"Antzelevitch","year":"2017","journal-title":"Europace"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Monasky, M.M., Micaglio, E., Ciconte, G., and Pappone, C. (2020). Brugada Syndrome: Oligogenic or Mendelian Disease?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051687"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3389\/fcvm.2018.00161","article-title":"Electrophysiological Basis for Early Repolarization Syndrome","volume":"5","author":"Sieira","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1161\/01.CIR.96.6.2038","article-title":"Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade des pointes in LQT2 and LQT3 models of the long-QT syndrome","volume":"96","author":"Shimizu","year":"1997","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/j.1748-1716.2007.01822.x","article-title":"Mouse models of human arrhythmia syndromes","volume":"192","author":"Killeen","year":"2008","journal-title":"Acta Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1253\/circj.CJ-15-0322","article-title":"Unveiling specific triggers and precipitating factors for fatal cardiac events in inherited arrhythmia syndromes","volume":"79","author":"Nakajima","year":"2015","journal-title":"Circ. J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pourrier, M., and Fedida, D. (2020). The Emergence of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) as a Platform to Model Arrhythmogenic Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020657"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1016\/j.hrthm.2015.05.032","article-title":"Enhanced fast-inactivated state stability of cardiac sodium channels by a novel voltage sensor SCN5A mutation, R1632C, as a cause of atypical Brugada syndrome","volume":"12","author":"Nakajima","year":"2015","journal-title":"Heart Rhythm"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nakajima, T., Dharmawan, T., Kawabata-Iwakawa, R., Tamura, S., Hasegawa, H., Kobari, T., Kaneko, Y., Nishiyama, M., and Kurabayashi, M. (2020). Biophysical defects of an SCN5A V1667I mutation associated with epinephrine-induced marked QT prolongation. J. Cardiovasc. Electrophysiol.","DOI":"10.1111\/jce.14575"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nakajima, T., Dharmawan, T., Kawabata-Iwakawa, R., Tamura, S., Hasegawa, H., Kobari, T., Ota, M., Tange, S., Nishiyama, M., and Kaneko, Y. (2021). Reduced current density, partially rescued by mexiletine, and depolarizing shift in activation of SCN5A W374G channels as a cause of severe form of Brugada syndrome. Ann. Noninvasive Electrocardiol., e12828.","DOI":"10.1111\/anec.12828"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1536\/ihj.20-203","article-title":"Novel Cardiocerebral Channelopathy Associated with a KCND3 V392I Mutation","volume":"61","author":"Nakajima","year":"2020","journal-title":"Int. Heart J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1016\/j.jacc.2008.02.068","article-title":"Long QT syndrome","volume":"51","author":"Goldenberg","year":"2008","journal-title":"J. Am. Coll Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1161\/CIRCULATIONAHA.109.863209","article-title":"Prevalence of the congenital long-QT syndrome","volume":"120","author":"Schwartz","year":"2009","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/ng0196-17","article-title":"Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias","volume":"12","author":"Wang","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0092-8674(95)90340-2","article-title":"A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel","volume":"81","author":"Sanguinetti","year":"1995","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/376683a0","article-title":"Molecular mechanism for an inherited cardiac arrhythmia","volume":"376","author":"Bennett","year":"1995","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/nature01335","article-title":"Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death","volume":"421","author":"Mohler","year":"2003","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/ng1197-338","article-title":"Mutations in the hminK gene cause long QT syndrome and suppress IKs function","volume":"17","author":"Splawski","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0092-8674(00)80728-X","article-title":"MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia","volume":"97","author":"Abbott","year":"1999","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0092-8674(01)00342-7","article-title":"Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen\u2019s syndrome","volume":"105","author":"Plaster","year":"2001","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cell.2004.09.011","article-title":"Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism","volume":"119","author":"Splawski","year":"2004","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1161\/CIRCULATIONAHA.106.635268","article-title":"Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome","volume":"114","author":"Vatta","year":"2006","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1161\/CIRCULATIONAHA.106.659086","article-title":"SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome","volume":"116","author":"Kaku","year":"2007","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20990","DOI":"10.1073\/pnas.0710527105","article-title":"Mutation of an A-kinase-anchoring protein causes long-QT syndrome","volume":"104","author":"Chen","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9355","DOI":"10.1073\/pnas.0801294105","article-title":"Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex","volume":"105","author":"Ueda","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.ajhg.2010.04.017","article-title":"Identification of a Kir3.4 mutation in congenital long QT syndrome","volume":"86","author":"Yang","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1161\/CIRCULATIONAHA.112.001216","article-title":"Calmodulin mutations associated with recurrent cardiac arrest in infants","volume":"127","author":"Crotti","year":"2013","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.hrthm.2014.10.035","article-title":"CALM3 mutation associated with long QT syndrome","volume":"12","author":"Reed","year":"2015","journal-title":"Heart Rhythm"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1161\/CIRCULATIONAHA.115.015397","article-title":"Homozygous\/Compound Heterozygous Triadin Mutations Associated With Autosomal-Recessive Long-QT Syndrome and Pediatric Sudden Cardiac Arrest: Elucidation of the Triadin Knockout Syndrome","volume":"131","author":"Altmann","year":"2015","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1161\/CIRCULATIONAHA.119.043132","article-title":"An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome","volume":"141","author":"Adler","year":"2020","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e009884","DOI":"10.1161\/JAHA.118.009884","article-title":"Genetics of Atrial Fibrillation","volume":"7","author":"Feghaly","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e002293","DOI":"10.1161\/CIRCGEN.118.002293","article-title":"Nocturnal Atrial Fibrillation Caused by Mutation in KCND2, Encoding Pore-Forming (alpha) Subunit of the Cardiac Kv4.2 Potassium Channel","volume":"11","author":"Drabkin","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1161\/CIRCULATIONAHA.118.036761","article-title":"Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation","volume":"139","author":"Yamada","year":"2019","journal-title":"Circulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1161\/01.CIR.103.1.89","article-title":"Genotype-phenotype correlation in the long-QT syndrome: Gene-specific triggers for life-threatening arrhythmias","volume":"103","author":"Schwartz","year":"2001","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1161\/01.CIR.101.6.616","article-title":"Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome","volume":"101","author":"Moss","year":"2000","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1161\/CIRCULATIONAHA.116.021823","article-title":"Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study","volume":"134","author":"Wilde","year":"2016","journal-title":"Circulation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/384078a0","article-title":"K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current","volume":"384","author":"Barhanin","year":"1996","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/384080a0","article-title":"Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel","volume":"384","author":"Sanguinetti","year":"1996","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1073\/pnas.89.2.554","article-title":"Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel","volume":"89","author":"Gellens","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1126\/science.1066843","article-title":"Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel","volume":"295","author":"Marx","year":"2002","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"C1131","DOI":"10.1152\/ajpcell.1989.256.6.C1131","article-title":"Isoproterenol, DBcAMP, and forskolin inhibit cardiac sodium current","volume":"256","author":"Ono","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/BF00371125","article-title":"The catalytic subunit of cyclic AMP-dependent protein kinase directly inhibits sodium channel activities in guinea-pig ventricular myocytes","volume":"419","author":"Sunami","year":"1991","journal-title":"Pflugers Arch."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1161\/01.RES.70.1.199","article-title":"Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation","volume":"70","author":"Matsuda","year":"1992","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.hrthm.2015.08.021","article-title":"Cardiac sodium channel mutation associated with epinephrine-induced QT prolongation and sinus node dysfunction","volume":"13","author":"Chen","year":"2016","journal-title":"Heart Rhythm"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3389\/fcell.2020.00761","article-title":"Propranolol Attenuates Late Sodium Current in a Long QT Syndrome Type 3-Human Induced Pluripotent Stem Cell Model","volume":"8","author":"Hirose","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_48","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":"ref_49","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/S0002-9149(99)00458-0","article-title":"Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with the long QT syndrome","volume":"84","author":"Moss","year":"1999","journal-title":"Am. J. Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0735-1097(98)00578-6","article-title":"Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1)","volume":"33","author":"Wilde","year":"1999","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1096\/fj.02-0200fje","article-title":"ERG K+ channel blockade enhances firing and epinephrine secretion in rat chromaffin cells: The missing link to LQT2-related sudden death?","volume":"17","author":"Gullo","year":"2003","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.jacc.2006.09.054","article-title":"Long QT syndrome and pregnancy","volume":"49","author":"Seth","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1093\/eurheartj\/ehx394","article-title":"Identification of a targeted and testable antiarrhythmic therapy for long-QT syndrome type 2 using a patient-specific cellular model","volume":"39","author":"Mehta","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_54","first-page":"2552","article-title":"Fever-induced QTc prolongation and ventricular arrhythmias in individuals with type 2 congenital long QT syndrome","volume":"118","author":"Amin","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1161\/01.CIR.88.4.1826","article-title":"Cellular electrophysiological effects of hyperthermia on isolated guinea pig papillary muscle. Implications for catheter ablation","volume":"88","author":"Nath","year":"1993","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1161\/01.RES.83.4.415","article-title":"Novel mechanism of HERG current suppression in LQT2: Shift in voltage dependence of HERG inactivation","volume":"83","author":"Nakajima","year":"1998","journal-title":"Circ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1161\/CIRCGENETICS.111.962316","article-title":"Phenotype variability in patients carrying KCNJ2 mutations","volume":"5","author":"Kimura","year":"2012","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1172\/JCI15183","article-title":"Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)","volume":"110","author":"Jensen","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jelectrocard.2008.02.023","article-title":"Oral verapamil effectively suppressed complex ventricular arrhythmias and unmasked U waves in a patient with Andersen-Tawil syndrome","volume":"41","author":"Erdogan","year":"2008","journal-title":"J. Electrocardiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1093\/europace\/eut160","article-title":"Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients related to KCNJ2 mutation","volume":"15","author":"Delannoy","year":"2013","journal-title":"Europace"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.hrthm.2014.12.009","article-title":"Efficacy and safety of flecainide for ventricular arrhythmias in patients with Andersen-Tawil syndrome with KCNJ2 mutations","volume":"12","author":"Miyamoto","year":"2015","journal-title":"Heart Rhythm"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1093\/europace\/euu063","article-title":"Long QT syndrome type 8: Novel CACNA1C mutations causing QT prolongation and variant phenotypes","volume":"16","author":"Fukuyama","year":"2014","journal-title":"Europace"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.yjmcc.2015.01.002","article-title":"Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome","volume":"80","author":"Wemhoner","year":"2015","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8089","DOI":"10.1073\/pnas.0502506102","article-title":"Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations","volume":"102","author":"Splawski","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.hrthm.2006.04.024","article-title":"Verapamil decreases ventricular tachyarrhythmias in a patient with Timothy syndrome (LQT8)","volume":"3","author":"Jacobs","year":"2006","journal-title":"Heart Rhythm"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.hrthm.2006.12.046","article-title":"Cellular basis for the electrocardiographic and arrhythmic manifestations of Timothy syndrome: Effects of ranolazine","volume":"4","author":"Sicouri","year":"2007","journal-title":"Heart Rhythm"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1111\/j.1540-8159.2010.02913.x","article-title":"Ranolazine safely decreases ventricular and atrial fibrillation in Timothy syndrome (LQT8)","volume":"35","author":"Shah","year":"2012","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1161\/CIRCEP.113.000092","article-title":"Inhibition of late sodium current by mexiletine: A novel pharmotherapeutical approach in timothy syndrome","volume":"6","author":"Gao","year":"2013","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.stemcr.2017.05.028","article-title":"Inhibition of CDK5 Alleviates the Cardiac Phenotypes in Timothy Syndrome","volume":"9","author":"Song","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1093\/hmg\/ddx073","article-title":"Allele-specific ablation rescues electrophysiological abnormalities in a human iPS cell model of long-QT syndrome with a CALM2 mutation","volume":"26","author":"Yamamoto","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/cvr\/cvx006","article-title":"Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes","volume":"113","author":"Rocchetti","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1161\/CIRCEP.109.862649","article-title":"Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome","volume":"2","author":"Itoh","year":"2009","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1093\/eurheartj\/ehv695","article-title":"The genetics underlying acquired long QT syndrome: Impact for genetic screening","volume":"37","author":"Itoh","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1161\/CIRCRESAHA.119.315209","article-title":"Towards Precision Medicine With Human iPSCs for Cardiac Channelopathies","volume":"125","author":"Wu","year":"2019","journal-title":"Circ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.stemcr.2020.10.005","article-title":"Isogenic Sets of hiPSC-CMs Harboring Distinct KCNH2 Mutations Differ Functionally and in Susceptibility to Drug-Induced Arrhythmias","volume":"15","author":"Brandao","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1159\/000047299","article-title":"Idiopathic short QT interval: A new clinical syndrome?","volume":"94","author":"Gussak","year":"2000","journal-title":"Cardiology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1161\/01.CIR.0000130409.72142.FE","article-title":"Mutation in the KCNQ1 gene leading to the short QT-interval syndrome","volume":"109","author":"Bellocq","year":"2004","journal-title":"Circulation"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1161\/01.CIR.0000109482.92774.3A","article-title":"Sudden death associated with short-QT syndrome linked to mutations in HERG","volume":"109","author":"Brugada","year":"2004","journal-title":"Circulation"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1161\/01.RES.0000162101.76263.8c","article-title":"A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene","volume":"96","author":"Priori","year":"2005","journal-title":"Circ. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1161\/CIRCULATIONAHA.106.668392","article-title":"Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death","volume":"115","author":"Antzelevitch","year":"2007","journal-title":"Circulation"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1038\/s41467-017-01630-0","article-title":"Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome","volume":"8","author":"Thorsen","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1016\/j.hrthm.2010.08.026","article-title":"Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death","volume":"7","author":"Burashnikov","year":"2010","journal-title":"Heart Rhythm"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13041-020-00634-0","article-title":"Genetic associations between voltage-gated calcium channels and autism spectrum disorder: A systematic review","volume":"13","author":"Liao","year":"2020","journal-title":"Mol. Brain."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Endres, D., Decher, N., Rohr, I., Vowinkel, K., Domschke, K., Komlosi, K., Tzschach, A., Glaser, B., Schiele, M.A., and Runge, K. (2020). New Cav1.2 Channelopathy with High-Functioning Autism, Affective Disorder, Severe Dental Enamel Defects, a Short QT Interval, and a Novel CACNA1C Loss-Of-Function Mutation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228611"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1016\/j.jacc.2017.10.025","article-title":"Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome","volume":"70","author":"Mazzanti","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"771","DOI":"10.3389\/fphar.2019.00771","article-title":"Impact of Antiarrhythmic Drugs on the Outcome of Short QT Syndrome","volume":"10","author":"Besler","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/0735-1097(92)90253-J","article-title":"Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. A multicenter report","volume":"20","author":"Brugada","year":"1992","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1053\/euhj.1998.1332","article-title":"The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome","volume":"20","author":"Matsuo","year":"1999","journal-title":"Eur. Heart J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/32675","article-title":"Genetic basis and molecular mechanism for idiopathic ventricular fibrillation","volume":"392","author":"Chen","year":"1998","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1161\/CIRCULATIONAHA.107.704627","article-title":"Molecular and functional characterization of novel glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) mutations in sudden infant death syndrome","volume":"116","author":"Valdivia","year":"2007","journal-title":"Circulation"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1161\/CIRCULATIONAHA.107.703330","article-title":"Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias","volume":"116","author":"London","year":"2007","journal-title":"Circulation"},{"key":"ref_92","first-page":"2260","article-title":"Sodium channel beta1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans","volume":"118","author":"Watanabe","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1161\/CIRCEP.107.748103","article-title":"Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome","volume":"1","author":"Delpon","year":"2008","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1161\/CIRCGENETICS.108.829192","article-title":"A mutation in the beta 3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype","volume":"2","author":"Hu","year":"2009","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.hrthm.2010.06.016","article-title":"Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes","volume":"7","author":"Tan","year":"2010","journal-title":"Heart Rhythm"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.hrthm.2011.02.021","article-title":"Transient outward current (I(to)) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome","volume":"8","author":"Giudicessi","year":"2011","journal-title":"Heart Rhythm"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1161\/CIRCGENETICS.110.959130","article-title":"MOG1: A new susceptibility gene for Brugada syndrome","volume":"4","author":"Kattygnarath","year":"2011","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1161\/CIRCEP.110.959619","article-title":"KCNE5 (KCNE1L) variants are novel modulators of Brugada syndrome and idiopathic ventricular fibrillation","volume":"4","author":"Ohno","year":"2011","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1161\/CIRCEP.111.969972","article-title":"A novel disease gene for Brugada syndrome: Sarcolemmal membrane-associated protein gene mutations impair intracellular trafficking of hNav1.5","volume":"5","author":"Ishikawa","year":"2012","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ijcard.2013.12.084","article-title":"ABCC9 is a novel Brugada and early repolarization syndrome susceptibility gene","volume":"171","author":"Hu","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1002\/humu.22328","article-title":"A missense mutation in the sodium channel beta2 subunit reveals SCN2B as a new candidate gene for Brugada syndrome","volume":"34","author":"Riuro","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1016\/j.hrthm.2013.09.064","article-title":"FGF12 is a candidate Brugada syndrome locus","volume":"10","author":"Hennessey","year":"2013","journal-title":"Heart Rhythm"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/ng.2712","article-title":"Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death","volume":"45","author":"Bezzina","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Liu, H., Chatel, S., Simard, C., Syam, N., Salle, L., Probst, V., Morel, J., Millat, G., Lopez, M., and Abriel, H. (2013). Molecular genetics and functional anomalies in a series of 248 Brugada cases with 11 mutations in the TRPM4 channel. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054131"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1161\/CIRCULATIONAHA.113.003077","article-title":"Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype","volume":"129","author":"Cerrone","year":"2014","journal-title":"Circulation"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1161\/CIRCRESAHA.115.303657","article-title":"Characterization of SEMA3A-encoded semaphorin as a naturally occurring Kv4.3 protein inhibitor and its contribution to Brugada syndrome","volume":"115","author":"Boczek","year":"2014","journal-title":"Circ. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jacc.2014.04.032","article-title":"Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome","volume":"64","author":"Hu","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s00424-016-1870-1","article-title":"Mutation in S6 domain of HCN4 channel in patient with suspected Brugada syndrome modifies channel function","volume":"468","author":"Biel","year":"2016","journal-title":"Pflugers Arch."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1161\/CIRCULATIONAHA.118.035070","article-title":"Reappraisal of Reported Genes for Sudden Arrhythmic Death: Evidence-Based Evaluation of Gene Validity for Brugada Syndrome","volume":"138","author":"Hosseini","year":"2018","journal-title":"Circulation"},{"key":"ref_110","first-page":"H369","article-title":"Transmural heterogeneity of action potentials and Ito1 in myocytes isolated from the human right ventricle","volume":"275","author":"Li","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.yjmcc.2009.07.013","article-title":"Molecular determinants of cardiac transient outward potassium current (I(to)) expression and regulation","volume":"48","author":"Niwa","year":"2010","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1046\/j.1540-8167.2001.00268.x","article-title":"The Brugada syndrome: Ionic basis and arrhythmia mechanisms","volume":"12","author":"Antzelevitch","year":"2001","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1161\/01.CIR.93.1.168","article-title":"Regional differences in current density and rate-dependent properties of the transient outward current in subepicardial and subendocardial myocytes of human left ventricle","volume":"93","author":"Nabauer","year":"1996","journal-title":"Circulation"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41586-020-1947-z","article-title":"Mechanism of adrenergic CaV1.2 stimulation revealed by proximity proteomics","volume":"577","author":"Liu","year":"2020","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1161\/CIRCULATIONAHA.117.027983","article-title":"Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry","volume":"135","author":"Yamagata","year":"2017","journal-title":"Circulation"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1016\/j.jacc.2005.08.043","article-title":"High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations","volume":"46","author":"Makiyama","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e009387","DOI":"10.1161\/JAHA.118.009387","article-title":"Sex-Dependent Phenotypic Variability of an SCN5A Mutation: Brugada Syndrome and Sick Sinus Syndrome","volume":"7","author":"Aizawa","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_118","first-page":"2219","article-title":"The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome","volume":"118","author":"Makita","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1161\/01.CIR.0000144458.58660.BB","article-title":"SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia","volume":"110","author":"McNair","year":"2004","journal-title":"Circulation"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.ymgme.2007.10.009","article-title":"SCN5A variants in Japanese patients with left ventricular noncompaction and arrhythmia","volume":"93","author":"Shan","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jelectrocard.2021.01.019","article-title":"Multiple arrhythmic and cardiomyopathic phenotypes associated with an SCN5A A735E mutation","volume":"65","author":"Sasaki","year":"2021","journal-title":"J. Electrocardiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1046\/j.1460-9592.2002.t01-1-00856.x","article-title":"Brugada-like electrocardiographic pattern induced by fever","volume":"25","author":"Saura","year":"2002","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.cardiores.2005.03.024","article-title":"Brugada syndrome and fever: Genetic and molecular characterization of patients carrying SCN5A mutations","volume":"67","author":"Keller","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cardiores.2006.02.030","article-title":"A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation","volume":"70","author":"Keller","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1161\/CIRCULATIONAHA.120.045720","article-title":"In Children and Adolescents From Brugada Syndrome-Families, Only SCN5A Mutation Carriers Develop a Type-1 ECG Pattern Induced By Fever","volume":"142","author":"Peltenburg","year":"2020","journal-title":"Circulation"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0896-6273(00)80680-7","article-title":"Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation","volume":"22","author":"Cha","year":"1999","journal-title":"Neuron"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0006-3495(99)76929-8","article-title":"The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4","volume":"77","author":"Sheets","year":"1999","journal-title":"Biophys. J."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1085\/jgp.201210935","article-title":"S1\u2013S3 counter charges in the voltage sensor module of a mammalian sodium channel regulate fast inactivation","volume":"141","author":"Groome","year":"2013","journal-title":"J. Gen. Physiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/19336950.2019.1649521","article-title":"Role of the voltage sensor module in Nav domain IV on fast inactivation in sodium channelopathies: The implication of closed-state inactivation","volume":"13","author":"Nakajima","year":"2019","journal-title":"Channels"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.yjmcc.2019.03.023","article-title":"Enhanced closed-state inactivation of mutant cardiac sodium channels (SCN5A N1541D and R1632C) through different mechanisms","volume":"130","author":"Dharmawan","year":"2019","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1016\/j.jacc.2016.07.779","article-title":"Patient-Specific and Genome-Edited Induced Pluripotent Stem Cell-Derived Cardiomyocytes Elucidate Single-Cell Phenotype of Brugada Syndrome","volume":"68","author":"Liang","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/0002-8703(93)90550-S","article-title":"Idiopathic ventricular fibrillation and bradycardia-dependent intraventricular block","volume":"126","author":"Aizawa","year":"1993","journal-title":"Am. Heart J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.hrthm.2006.05.016","article-title":"Characterization of J wave in a patient with idiopathic ventricular fibrillation","volume":"3","author":"Shinohara","year":"2006","journal-title":"Heart Rhythm"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1056\/NEJMoa071968","article-title":"Sudden cardiac arrest associated with early repolarization","volume":"358","author":"Haissaguerre","year":"2008","journal-title":"N Engl. J. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1161\/01.CIR.93.2.372","article-title":"Cellular basis for the electrocardiographic J wave","volume":"93","author":"Yan","year":"1996","journal-title":"Circulation"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1161\/CIRCEP.111.963983","article-title":"Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization","volume":"4","author":"Watanabe","year":"2011","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1161\/CIRCGENETICS.114.000623","article-title":"Evaluation of genes encoding for the transient outward current (Ito) identifies the KCND2 gene as a cause of J-wave syndrome associated with sudden cardiac death","volume":"7","author":"Perrin","year":"2014","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/j.hrthm.2019.05.033","article-title":"A de novo gain-of-function KCND3 mutation in early repolarization syndrome","volume":"16","author":"Takayama","year":"2019","journal-title":"Heart Rhythm"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.hrthm.2014.05.001","article-title":"Combination therapy of cilostazol and bepridil suppresses recurrent ventricular fibrillation related to J-wave syndromes","volume":"11","author":"Shinohara","year":"2014","journal-title":"Heart Rhythm"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1152\/jn.1996.75.5.2174","article-title":"Cloning of a novel component of A-type K+ channels operating at subthreshold potentials with unique expression in heart and brain","volume":"75","author":"Serodio","year":"1996","journal-title":"J. Neurophysiol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1152\/jn.1998.79.2.1081","article-title":"Differential expression of Kv4 K+ channel subunits mediating subthreshold transient K+ (A-type) currents in rat brain","volume":"79","author":"Serodio","year":"1998","journal-title":"J. Neurophysiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1046\/j.1460-9568.2003.02786.x","article-title":"Contrasting expression of Kv4.3, an A-type K+ channel, in migrating Purkinje cells and other post-migratory cerebellar neurons","volume":"18","author":"Hsu","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/ana.23701","article-title":"Mutations in KCND3 cause spinocerebellar ataxia type 22","volume":"72","author":"Lee","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1002\/ana.23700","article-title":"Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19","volume":"72","author":"Duarri","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1093\/cvr\/cvt028","article-title":"A novel KCND3 gain-of-function mutation associated with early-onset of persistent lone atrial fibrillation","volume":"98","author":"Olesen","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1002\/humu.22058","article-title":"Novel mutations in the KCND3-encoded Kv4.3 K+ channel associated with autopsy-negative sudden unexplained death","volume":"33","author":"Giudicessi","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1093\/hmg\/ddu056","article-title":"Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation","volume":"23","author":"Lee","year":"2014","journal-title":"Hum. Mol. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3930\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:27:46Z","timestamp":1760365666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,10]]},"references-count":147,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22083930"],"URL":"https:\/\/doi.org\/10.3390\/ijms22083930","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,10]]}}}