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
Open accessAbstract
Background— Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death. Methods and Results— Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca vβ2b ), CACNA2D1 (Ca vα2δ1 ), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca v 1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours. Three probands displaying ST-segment elevation and corrected QT intervals ≤360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the α 1 - and β 2b -subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Ca v 1.2 channels but normal trafficking of channels containing G490R Ca v 1.2 or S481L Ca vβ2b -subunits. Conclusions— This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.
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AF prevalence in short QT syndrome is up to 70%.
“Short QT syndrome KCNH2 KCNQ1 KCNJ2 CACNA1C CACNB2b IKr IKs IK1 ICa ICa Up to 70% 853, 856-858”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [853]
AF prevalence in Brugada syndrome is 10-20%.
“Brugada syndrome SCN5A GPDIL SCN1B CACNA1C CACNB2b others INa INa INa ICa ICa others 10-20% 851-855”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [853]
AF prevalence ranges from 5% to 20% in patients with long QT syndrome or Brugada syndrome, and is up to 70% in short QT syndrome.
“AF prevalence ranges from 5% to 20% in patients with long QT syndrome or Brugada syndrome, and is up to 70% in short QT syndrome (Table 20).853,[856][857][858]”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [853]
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CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism
Splawski, I., Timothy, K. W., Sharpe, L. M., Decher, N., Kumar, P., Bloise, R., Napolitano, C., Schwartz, P. J., Joseph, R. M., Condouris, K., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.011 · Cited by 1,586 · cited 1× · see citing works
“val; (3) the 3 mutations are not observed in ethnically matched healthy individuals; and (4) there is a clear genotype-phenotype”
BackgroundSelf-citationSudden death associated with short-QT syndrome linked to mutations in HERG
Brugada, R., Hong, K., Dumaine, R., Cordeiro, J., Gaita, F., Borggrefe, M., Menendez, T. M., Brugada, J., Pollevick, G. D., Wolpert, C., et al. (2004) · Circulation · doi:10.1161/01.cir.0000109482.92774.3a · Cited by 847 · see citing works
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Research works printed but not linked: 31
- [1]Priori SG, Aliot E, Blomstrom-Lundqvist C, Bossaert L, Breithardt G, Brugada P, Camm JA, Cappato R, Cobbe SM, Di MC, Maron BJ, McKenna WJ, Pedersen AK, Ravens U, Schwartz PJ, Trusz-Gluza M, Vardas P, Wellens HJ, Zipes DP. Task Force on Sudden Cardiac Death, European Society of Cardiology. Europace. 2002;4:3–18. doi: 10.1053/eupc.2001.0214. [DOI] [PubMed] [Google Scholar] · DOI
- [2]Antzelevitch C. Molecular genetics of arrhythmias and cardiovascular conditions associated with arrhythmias. Heart Rhythm. 2004;1:42C–56C. doi: 10.1016/j.hrthm.2004.10.018. [DOI] [PubMed] [Google Scholar] · DOI
- [4]Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A. 2005;102:8089–8096. doi: 10.1073/pnas.0502506102. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- [5]Bichet D, Cornet V, Geib S, Carlier E, Volsen S, Hoshi T, Mori Y, De Waard M. The I-II loop of the Ca2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit. Neuron. 25:2000. 177–190. doi: 10.1016/s0896-6273(00)80881-8. [DOI] [PubMed] [Google Scholar] · DOI
- [6]Gussak I, Antzelevitch C, Goodman D, Bjerregaard P. Short QT interval: ECG phenomenon and clinical syndrome. In: Gussak I, Antzelevitch C, editors. Cardiac Repolarization: Bridging Basic and Clinical Sciences. Totowa, NJ: Humana Press; 2003. pp. 497–506. [Google Scholar]
- [8]Bellocq C, Van Ginneken AC, Bezzina CR, Alders M, Escande D, Mannens MM, Baro I, Wilde AA. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation. 2004;109:2394–2397. doi: 10.1161/01.CIR.0000130409.72142.FE. [DOI] [PubMed] [Google Scholar] · DOI
- [9]Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A, Napolitano C, Anumonwo J, Raffaele di BM, Gudapakkam S, Bosi G, Stramba-Badiale M, Jalife J. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res. 2005;96:800–807. doi: 10.1161/01.RES.0000162101.76263.8c. [DOI] [PubMed] [Google Scholar] · DOI
- [10]Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, Moya A, Borggrefe M, Breithardt G, Ortiz-Lopez R, Wang Z, Antzelevitch C, O’Brien RE, Schultze-Bahr E, Keating MT, Towbin JA, Wang Q. Genetic basis and molecular mechanisms for idiopathic ventricular fibrillation. Nature. 1998;392:293–296. doi: 10.1038/32675. [DOI] [PubMed] [Google Scholar] · DOI
- [11]Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P, Corrado D, Hauer RN, Kass RS, Nademanee K, Priori SG, Towbin JA. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation. 2002;106:2514–2519. doi: 10.1161/01.cir.0000034169.45752.4a. [DOI] [PubMed] [Google Scholar] · DOI
- [12]Antzelevitch C, Brugada P, Borggrefe J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A. Brugada syndrome: report of the Second Consensus Conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation. 2005;111:659–670. doi: 10.1161/01.CIR.0000152479.54298.51. [DOI] [PubMed] [Google Scholar] · DOI
- [13]Rautaharju PM, Zhou SH, Wong S, Calhoun HP, Berenson GS, Prineas R, Davignon A. Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol. 1992;8:690–695. [PubMed] [Google Scholar]
- [14]Viskin S, Zeltsner D, Ish-Shalom M, Katz A, Glikson M, Justo D, Tekes-Manova D, Belhassen B. Is idiopathic ventricular fibrillation a short QT syndrome? Comparison of QT intervals of patients with idiopathic ventricular fibrillation and healthy controls. Heart Rhythm. 2004;1:587–591. doi: 10.1016/j.hrthm.2004.07.010. [DOI] [PubMed] [Google Scholar] · DOI
- [15]Costantini DL, Arruda EP, Agarwal P, Kim KH, Zhu Y, Zhu W, Lebel M, Cheng CW, Park CY, Pierce SA, Guerchicoff A, Pollevick GD, Chan TY, Kabir MG, Cheng SH, Husain M, Antzelevitch C, Srivastava D, Gross GJ, Hui CC, Backx PH, Bruneau BG. The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Cell. 2005;123:347–358. doi: 10.1016/j.cell.2005.08.004. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [16]Kobrinsky E, Tiwari S, Maltsev VA, Harry JB, Lakatta E, Abernethy DR, Soldatov NM. Differential role of the alpha1C subunit tails in regulation of the Cav1.2 channel by membrane potential, beta subunits, and Ca2+ ions. J Biol Chem. 2005;280:12474–12485. doi: 10.1074/jbc.M412140200. [DOI] [PubMed] [Google Scholar] · DOI
- [17]Zuhlke RD, Bouron A, Soldatov NM, Reuter H. Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha 1C subunit gene. FEBS Lett. 1998;427:220–224. doi: 10.1016/s0014-5793(98)00425-6. [DOI] [PubMed] [Google Scholar] · DOI
- [18]Fish JM, Antzelevitch C. Role of sodium and calcium channel block in unmasking the Brugada syndrome. Heart Rhythm. 2004;1:210–217. doi: 10.1016/j.hrthm.2004.03.061. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [19]Shimizu W. Acquired forms of the Brugada syndrome. J Electrocardiol. 2005;38(suppl):22–25. doi: 10.1016/j.jelectrocard.2005.06.005. [DOI] [PubMed] [Google Scholar] · DOI
- [20]Hong K, Berruezo-Sanchez A, Poungvarin N, Oliva A, Vatta M, Brugada J, Brugada P, Towbin JA, Dumaine R, Pinero-Galvez C, Antzelevitch C, Brugada R. Phenotypic characterization of a large European family with Brugada syndrome displaying a sudden unexpected death syndrome mutation in SCN5A. J Cardiovasc Electrophysiol. 2004;15:64–69. doi: 10.1046/j.1540-8167.2004.03341.x. [DOI] [PubMed] [Google Scholar] · DOI
- [21]Extramiana F, Antzelevitch C. Amplified transmural dispersion of repolarization as the basis for arrhythmogenesis in a canine ventricular-wedge model of Short-QT syndrome. Circulation. 2004;110:3661–3666. doi: 10.1161/01.CIR.0000143078.48699.0C. [DOI] [PubMed] [Google Scholar] · DOI
- [22]Magnano AR, Holleran S, Ramakrishnan R, Reiffel JA, Bloomfield DM. Autonomic nervous system influences on QT interval in normal subjects. J Am Coll Cardiol. 2002;39:1820–1826. doi: 10.1016/s0735-1097(02)01852-1. [DOI] [PubMed] [Google Scholar] · DOI
- [23]Wolpert C, Schimpf R, Giustetto C, Antzelevitch C, Cordeiro J, Dumaine R, Brugada R, Hong K, Bauersfeld U, Gaita F, Borggrefe M. Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005;16:54–58. doi: 10.1046/j.1540-8167.2005.04470.x. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [24]Borggrefe M. Atrial tachyarrhythmias in Brugada syndrome. In: Antzelevitch C, Brugada P, Brugada J, Brugada R, editors. The Brugada Syndrome: From Bench to Bedside. Oxford, UK: Blackwell Futura; 2004. pp. 178–183. [Google Scholar]
- [25]Giustetto C, Di MF, Wolpert C, Borggrefe M, Schimpf R, Sbragia P, Leone G, Maury P, Anttonen O, Haissaguerre M, Gaita F. Short QT syndrome: clinical findings and diagnostic-therapeutic implications. Eur Heart J. 2006;27:2440–2447. doi: 10.1093/eurheartj/ehl185. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [26]Antzelevitch C, Brugada P, Brugada J, Brugada R, Nademanee K, Towbin JA. Clinical Approaches to Tachyarrhythmias The Brugada Syndrome. Armonk, NY: Futura; 1999. [Google Scholar]
- [27]Gaita F, Giustetto C, Bianchi F, Schimpf R, Haissaguerre M, Calo L, Brugada R, Antzelevitch C, Borggrefe M, Wolpert C. Short QT syndrome: pharmacological treatment. J Am Coll Cardiol. 2004;43:1494–1499. doi: 10.1016/j.jacc.2004.02.034. [DOI] [PubMed] [Google Scholar] · DOI
- [28]Belhassen B, Glick A, Viskin S. Efficacy of quinidine in high-risk patients with Brugada syndrome. Circulation. 2004;110:1731–1737. doi: 10.1161/01.CIR.0000143159.30585.90. [DOI] [PubMed] [Google Scholar] · DOI
- [29]Schulze-Bahr E, Eckardt L, Breithardt G, Seidl K, Wichter T, Wolpert C, Borggrefe M, Haverkamp W. Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease. Hum Mutat. 2003;21:651–652. doi: 10.1002/humu.9144. [DOI] [PubMed] [Google Scholar] · DOI
- [30]Wang Q, Shen J, Splawski I, Atkinson DL, Li ZZ, Robinson JL, Moss AJ, Towbin JA, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995;80:805–811. doi: 10.1016/0092-8674(95)90359-3. [DOI] [PubMed] [Google Scholar] · DOI
- [31]Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995;80:795–803. doi: 10.1016/0092-8674(95)90358-5. [DOI] [PubMed] [Google Scholar] · DOI
- [32]Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, Van Raay TJ, Shen J, Timothy KW, Vincent GM, De Jager T, Schwartz PJ, Towbin JA, Moss AJ, Atkinson DL, Landes GM, Connors TD, Keating MT. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996;12:17–23. doi: 10.1038/ng0196-17. [DOI] [PubMed] [Google Scholar] · DOI
- [33]London B, Sanyal S, Michalec M, Pfahnl AE, Shang LL, Kerchner BS, Lagana S, Aleong RG, Mehdi H, Gutmann R, Weiss R, Dudley SC. A mutation in the glycerol-3-phosphate dehydrogenase 1-like gene (GPD1L) causes Brugada syndrome. Heart Rhythm. 2006;3:S32. Abstract. [Google Scholar]
Cited by
Sorted by citations
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Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418 · see citing works
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P. F., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castellà, M., Diener, H., Heidbüchel, H., Hendriks, J., et al. (2016) · EP Europace · doi:10.1093/europace/euw295 · Cited by 6,438 · see citing works
Calkins, H., Kuck, K. H., Cappato, R., Brugada, J., Camm, A. J., Chen, S.-A., Crijns, H. J. G., Damiano, R. J., Davies, D. W., DiMarco, J., et al. (2012) · Europace · doi:10.1093/europace/eus027 · Cited by 2,722 · see citing works
Self-citationCalkins, H., Kuck, K., Cappato, R., Brugada, J., Camm, A., Chen, S.-A., Crijns, H., Damiano, R., Davies, D., Dimarco, J., et al. (2012) · Journal of interventional cardiac electrophysiology · doi:10.1007/s10840-012-9672-7 · Cited by 1,959 · see citing works
Self-citationPriori, S. G., Wilde, A. A., Horie, M., Cho, Y., Behr, E. R., Berul, C., Blom, N., Brugada, J., Chiang, C.-E., Huikuri, H., et al. (2013) · Heart Rhythm · doi:10.1016/j.hrthm.2013.05.014 · Cited by 1,942 · see citing works
“Often patients with mutations in these genes present a Type I Brugada Syndrome ECG either spontaneously or in response to drug challenge with Class I antiarrhythmic agents [141].”
Calkins, H., Kuck, K. H., Cappato, R., Brugada, J., Camm, A. J., Chen, S.-A., Crijns, H. J. G., Damiano, R. J., Davies, D. W., DiMarco, J., et al. (2012) · Heart Rhythm · doi:10.1016/j.hrthm.2011.12.016 · Cited by 1,456 · see citing works
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezw313 · Cited by 1,403 · see citing works
Genome-wide association study of blood pressure and hypertension
Levy, D., Ehret, G. B., Rice, K., Verwoert, G. C., Launer, L. J., Dehghan, A., Glazer, N. L., Morrison, A. C., Johnson, A. D., Aspelund, T., et al. (2009) · Nature Genetics · doi:10.1038/ng.384 · Cited by 1,364 · see citing works
“The gene is expressed in the heart and a nonsynomymous variant in CACNB2 was identified in affected individuals with Brugada syndrom”
BackgroundAckerman, M. J., Priori, S. G., Willems, S., Berul, C. I., Brugada, R., Calkins, H. G., Camm, A. J., Ellinor, P. T., Gollob, M. H., Hamilton, R. M., et al. (2011) · EP Europace · doi:10.1093/europace/eur245 · Cited by 881 · see citing works
Self-citationAckerman, M. J., Priori, S. G., Willems, S., Berul, C. I., Brugada, R., Calkins, H. G., Camm, A. J., Ellinor, P. T., Gollob, M. H., Hamilton, R. M., et al. (2011) · Heart Rhythm · doi:10.1016/j.hrthm.2011.05.020 · Cited by 1,472 · see citing works
“Clinical cases describing a type 1 Brugada ECG pattern and associated with short QT-intervals and genetic mutations within CACNA1C or CACNB2b have been rarely described and proposed to represent sub-types of SQTS.(142)”
Self-citationProbst, V., Veltmann, C., Eckardt, L., Meregalli, P. G., Gaita, F., Tan, H. L., Babuty, D., Sacher, F., Giustetto, C., Schulze-Bahr, E., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.887026 · Cited by 847 · see citing works
Self-citationPriori, S., Wilde, A., Horie, M., Cho, Y., Behr, E. R., Berul, C., Blom, N., Brugada, J., Chiang, C.-E., Huikuri, H., et al. (2014) · Journal of Arrhythmia · doi:10.1016/j.joa.2013.07.002 · Cited by 651 · see citing works
“Often patients with mutations in these genes present a type I Brugada syndrome ECG either spontaneously or in response to drug challenge with Class I antiarrhythmic agents [141].”
Sudden Cardiac Death Prediction and Prevention
Fishman, G. I., Chugh, S. S., Dimarco, J., Albert, C. M., Anderson, M. E., Bonow, R. O., Buxton, A. E., Chen, P., Estes, M., Jouven, X., et al. (2010) · Circulation · doi:10.1161/circulationaha.110.976092 · Cited by 609 · see citing works
T(p-e)/QT ratio as an index of arrhythmogenesis.
Gupta, P., Patel, C., Patel, H., Narayanaswamy, S., Malhotra, B., Green, J., & Yan, G.-X. (2008) · Journal of Electrocardiology · doi:10.1016/j.jelectrocard.2008.07.016 · Cited by 628 · see citing works
Risk Stratification in Brugada Syndrome
Priori, S. G., Gasparini, M., Napolitano, C., Della Bella, P., Ottonelli, A. G., Sassone, B., Giordano, U., Pappone, C., Mascioli, G., Rossetti, G., et al. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.08.064 · Cited by 581 · see citing works
Recent advances in the molecular pathophysiology of atrial fibrillation
Wakili, R., Voigt, N., Kääb, S., Dobrev, D., & Nattel, S. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46315 · Cited by 543 · see citing works
Antzelevitch, C., & Yan, G.-X. (2009) · Heart Rhythm · doi:10.1016/j.hrthm.2009.12.006 · Cited by 554 · see citing works
Self-citationWatanabe, H., Koopmann, T., Scouarnec, S. L., Yang, T., Ingram, C. R., Schott, J., Demolombe, S., Probst, V., Anselme, F., Escande, D., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33891 · Cited by 507 · see citing works
“have recently reported mutations in the gene encoding the L-type calcium channel (CACNA1C) or its β2b subunit (CACNB2b) in Brugada syndrome patients with unusually short QT intervals (14), but the frequency of these defects as a cause for more-typical Brugada syndrome is unknown.”
BackgroundSelf-citationJ-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge
Antzelevitch, C., Yan, G.-X., Ackerman, M., Borggrefe, M., Corrado, D., Guo, J.-H., Gussak, I., Hasdemir, C., Horie, M., Huikuri, H., et al. (2016) · Journal of Arrhythmia · doi:10.1016/j.joa.2016.07.002 · Cited by 462 · see citing works
“The QT interval is relatively short in patients with ERS,(2,113) and BrS who carry mutations in calcium channel genes.(114)”
Self-citationThe genetic basis of long QT and short QT syndromes: A mutation update
Hedley, P. L., Jørgensen, P., Schlamowitz, S., Wangari, R., Moolman‐Smook, J. C., Brink, P. A., Kanters, J. K., Corfield, V. A., & Christiansen, M. (2009) · Human Mutation · doi:10.1002/humu.21106 · Cited by 422 · see citing works
“Loss-of-function mutations in CACNA1C [Antzelevitch et al., 2007d] and CACNB2 [Antzelevitch et al., 2007d], encoding the a- and b2-subunits of the Cav1.”
BackgroundInfluentialBurashnikov, E., Pfeiffer, R., Barajas-Martinez, H., Delpón, E., Hu, D., Desai, M., Borggrefe, M., Haïssaguerre, M., Kanter, R., Pollevick, G., et al. (2010) · Heart Rhythm · doi:10.1016/j.hrthm.2010.08.026 · Cited by 438 · see citing works
“In addition, CD8 cDNA was cotransfected as a reporter gene for the experiment involving p.D601E CACNB2b.”
BackgroundMethodResultInfluentialSelf-citationLondon, B., Michalec, M., Mehdi, H., Zhu, X., Kerchner, L., Sanyal, S., Viswanathan, P. C., Pfahnl, A. E., Shang, L. L., Madhusudanan, M., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.703330 · Cited by 437 · see citing works
The β Subunit of Voltage-Gated Ca2+ Channels
Buraei, Z., & Yang, J. (2010) · Physiological Reviews · doi:10.1152/physrev.00057.2009 · Cited by 406 · see citing works
Overview of Basic Mechanisms of Cardiac Arrhythmia
Antzelevitch, C. N., & Burashnikov, A. (2011) · Cardiac Electrophysiology Clinics · doi:10.1016/j.ccep.2010.10.012 · Cited by 472 · see citing works
Self-citationFunctional Effects of KCNE3 Mutation and its Role in the Development of Brugada Syndrome
Delpón, E., Cordeiro, J., Núñez, L., Thomsen, P. E., Guerchicoff, A., Pollevick, G., Wu, Y.-S., Kanters, J. K., Larsen, C., Hofman-Bang, J., et al. (2008) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.107.748103 · Cited by 357 · see citing works
Self-citationThe short QT syndrome: proposed diagnostic criteria.
Gollob, M., Redpath, C., & Roberts, J. D. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.09.048 · Cited by 330 · see citing works
L-type CaV1.2 calcium channels: from in vitro findings to in vivo function.
Hofmann, F., Flockerzi, V., Kahl, S., & Wegener, J. (2014) · Physiological Reviews · doi:10.1152/physrev.00016.2013 · Cited by 330 · see citing works
“2 1 gene (A39V and G490R, Brugada syndrome-3) or in the N4 encoding exon of the CaV 2 gene (S481L, Brugada syndrome-4) (8, 96).”
BackgroundSCN5A Mutations and the Role of Genetic Background in the Pathophysiology of Brugada Syndrome
Probst, V., Wilde, A., Barc, J., Sacher, F., Babuty, D., Mabo, P., Mansourati, J., Scouarnec, S. L., Kyndt, F., Caignec, C. L., et al. (2009) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.109.853374 · Cited by 329 · see citing works
Long-Term Follow-Up of Patients With Short QT Syndrome
Giustetto, C., Schimpf, R., Mazzanti, A., Scrocco, C., Maury, P., Anttonen, O., Probst, V., Blanc, J.-J., Sbragia, P., Dalmasso, P., et al. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.03.038 · Cited by 325 · see citing works
“A family had a mutation in CACNB2b (8).”
InfluentialSelf-citationThe QT syndromes: long and short
Morita, H., Wu, J., & Zipes, D. P. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61307-0 · Cited by 311 · see citing works
Impact of Genetics on the Clinical Management of Channelopathies
Schwartz, P., Ackerman, M., George, A., & Wilde, A. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.04.044 · Cited by 324 · see citing works
“Calcium channel–related BrS seems to associate with shorter-than-normal QTc intervals, but it is not clear whether this affects prognosis (83).”
BackgroundGenetics of sudden cardiac death.
Bezzina, C., Lahrouchi, N., & Priori, S. (2015) · Circulation Research · doi:10.1161/circresaha.116.304030 · Cited by 298 · see citing works
“cium channel subunits CACNA1C or CACNB2 can cause an overlapping phenotype of BrS and SQTS .(78) BrS-causing mu-”
BackgroundAntzelevitch, C. N. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00355.2007 · Cited by 263 · see citing works
Self-citationA Mutation in the β3 Subunit of the Cardiac Sodium Channel Associated with Brugada ECG Phenotype
Hu, D., Barajas-Martinez, H., Burashnikov, E., Springer, M., Wu, Y.-S., Varró, A., Pfeiffer, R., Koopmann, T., Cordeiro, J., Guerchicoff, A., et al. (2009) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.108.829192 · Cited by 277 · see citing works
Self-citationGrant, A. (2009) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.108.789081 · Cited by 254 · see citing works
Reappraisal of Reported Genes for Sudden Arrhythmic Death
Hosseini, S. M., Kim, R., Udupa, S., Costain, G., Jobling, R., Liston, E., Jamal, S. M., Szybowska, M., Morel, C. F., Bowdin, S., et al. (2018) · Circulation · doi:10.1161/circulationaha.118.035070 · Cited by 239 · see citing works
J Wave Syndromes Consensus Conference: Emerging Concepts & Gaps in Knowledge
Antzelevitch, C., Yan, G.-X., Ackerman, M., Borggrefe, M., Corrado, D., Guo, J.-H., Gussak, I., Hasdemir, C., Horie, M., Huikuri, H., et al. (2016) · Heart Rhythm · doi:10.1016/j.hrthm.2016.05.024 · Cited by 239 · see citing works
Self-citationNattel, S., & Dobrev, D. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs079 · Cited by 221 · see citing works
Novel Insight Into the Natural History of Short QT Syndrome
Mazzanti, A., Kanthan, A., Monteforte, N., Memmi, M., Bloise, R., Novelli, V., Miceli, C., O’Rourke, S., Borio, G., Zienciuk-Krajka, A., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.09.078 · Cited by 220 · see citing works
“Screening of CACNA1C and CACNB2 genes was performed after the link between mutations in the 2 genes was reported in the published data (9).”
BackgroundVarró, A., Tomek, J., Nagy, N., Virág, L., Passini, E., Rodríguez, B., & Baczkó, I. (2020) · Physiological Reviews · doi:10.1152/physrev.00024.2019 · Cited by 219 · see citing works
Wilde, A. A. M., Semsarian, C., Márquez, M. F., Shamloo, A. S., Ackerman, M. J., Ashley, E. A., Sternick, E. B., Barajas-Martínez, H., Behr, E. R., Bezzina, C. R., et al. (2022) · EP Europace · doi:10.1093/europace/euac030 · Cited by 399 · see citing works
“Loss of function type mutations in L-type calcium channel related genes, CACNA1C, CACNA2b,(224) and CACNA2D1(218) have been linked to SQTS(17) (Supplementary material online, Table S10), frequently showing overlapping BrS features.(224) However, the evidence of these genes is limited at most.”
BackgroundCrotti, L., Marcou, C. A., Tester, D., Castelletti, S., Giudicessi, J., Torchio, M., Medeiros-Domingo, A., Simone, S., Will, M. L., Dagradi, F., et al. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.04.037 · Cited by 214 · see citing works
STRIPAK Complexes: structure, biological function, and involvement in human diseases
Hwang, J., & Pallas, D. (2013) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2013.11.021 · Cited by 210 · see citing works
Tester, D., & Ackerman, M. (2011) · Circulation · doi:10.1161/circulationaha.109.914838 · Cited by 201 · see citing works
L-type Ca(2+) current in ventricular cardiomyocytes.
Bénitah, J., Alvarez, J., & Gómez, A. (2010) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.07.026 · Cited by 197 · see citing works
“Brugada type I ECG pattern [176].”
Templin, C., Ghadri, J., Rougier, J., Baumer, A., Kaplan, V., Albesa, M., Sticht, H., Rauch, A., Puleo, C., Hu, D., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr076 · Cited by 196 · see citing works
Self-citationSchwartz, P., Ackerman, M., Antzelevitch, C., Bezzina, C., Borggrefe, M., Cuneo, B., & Wilde, A. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-0188-7 · Cited by 193 · see citing works
Self-citationGenetic testing for inherited cardiac disease
Wilde, A., & Behr, E. (2013) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2013.108 · Cited by 192 · see citing works
Inherited calcium channelopathies in the pathophysiology of arrhythmias
Venetucci, L., Denegri, M., Napolitano, C., & Priori, S. (2012) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2012.93 · Cited by 188 · see citing works
The genetic basis of Brugada syndrome: A mutation update
Hedley, P., Jørgensen, P., Schlamowitz, S., Moolman-Smook, J., Kanters, J. K., Corfield, V., & Christiansen, M. (2009) · Human Mutation · doi:10.1002/humu.21066 · Cited by 184 · see citing works
Catalano, O., Antonaci, S., Moro, G., Mussida, M., Frascaroli, M., Baldi, M., Cobelli, F., Baiardi, P., Nastoli, J., Bloise, R., et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp252 · Cited by 184 · see citing works
Bartos, D. C., Grandi, E., & Ripplinger, C. M. (2015) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2015.tb00647.x · Cited by 178 · see citing works
The QT interval: too long, too short or just right.
Viskin, S. (2009) · Heart Rhythm · doi:10.1016/j.hrthm.2009.02.044 · Cited by 177 · see citing works
Watanabe, H., Nogami, A., Ohkubo, K., Kawata, H., Hayashi, Y., Ishikawa, T., Makiyama, T., Nagao, S., Yagihara, N., Takehara, N., et al. (2011) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.111.963983 · Cited by 176 · see citing works
Self-citationWilde, A. A. M., Semsarian, C., Márquez, M. F., Shamloo, A. S., Ackerman, M. J., Ashley, E. A., Sternick, E. B., Barajas-Martínez, H., Behr, E. R., Bezzina, C. R., et al. (2022) · Heart Rhythm · doi:10.1016/j.hrthm.2022.03.1225 · Cited by 281 · see citing works
MOG1: A New Susceptibility Gene for Brugada Syndrome
Kattygnarath, D., Maugenre, S., Neyroud, N., Balse, E., Ichai, C., Denjoy, I., Dilanian, G., Martins, R. P., Fressart, V., Berthet, M., et al. (2011) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.110.959130 · Cited by 173
Heterogeneity and cardiac arrhythmias: An overview
Antzelevitch, C. N. (2007) · Heart Rhythm · doi:10.1016/j.hrthm.2007.03.036 · Cited by 180 · see citing works
Self-citationGenetic, Molecular and Cellular Mechanisms Underlying the J Wave Syndromes
Antzelevitch, C. (2012) · Circulation Journal · doi:10.1253/circj.cj-12-0284 · Cited by 168 · see citing works
Self-citationBerne, P., & Brugada, J. (2012) · Circulation Journal · doi:10.1253/circj.cj-12-0717 · Cited by 167 · see citing works
Hoogendijk, M., Opthof, T., Postema, P., Wilde, A., de Bakker, J., & Coronel, R. (2010) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.110.937029 · Cited by 167 · see citing works
SCN5A channelopathies--an update on mutations and mechanisms.
Zimmer, T., & Surber, R. (2008) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2008.10.005 · Cited by 165 · see citing works
High prevalence of early repolarization in short QT syndrome.
Watanabe, H., Makiyama, T., Koyama, T., Kannankeril, P., Seto, S., Okamura, K., Oda, H., Itoh, H., Okada, M., Tanabe, N., et al. (2010) · Heart Rhythm · doi:10.1016/j.hrthm.2010.01.012 · Cited by 160 · see citing works
Self-citationGollob, M., Blier, L., Brugada, R., Champagne, J., Chauhan, V., Connors, S., Gardner, M., Green, M., Gow, R., Hamilton, R., et al. (2011) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2010.12.078 · Cited by 157 · see citing works
J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge.
Antzelevitch, C., Yan, G.-X., Ackerman, M., Borggrefe, M., Corrado, D., Guo, J.-H., Gussak, I., Hasdemir, C., Horie, M., Huikuri, H., et al. (2016) · Europace · doi:10.1093/europace/euw235 · Cited by 155 · see citing works
“The QT interval is relatively short in patients with ERS [2,113], and BrS who carry mutations in calcium channel genes [114].”
BackgroundSelf-citationJuang, J., & Horie, M. (2016) · Journal of Arrhythmia · doi:10.1016/j.joa.2016.07.012 · Cited by 153 · see citing works
L-type calcium channel targeting and local signalling in cardiac myocytes.
Shaw, R., & Colecraft, H. M. (2013) · Cardiovascular Research · doi:10.1093/cvr/cvt021 · Cited by 150 · see citing works
Short QT Syndrome: From Bench to Bedside
Patel, C., Yan, G.-X., & Antzelevitch, C. (2010) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.109.921056 · Cited by 150 · see citing works
Self-citationThe hERG K+ channel: target and antitarget strategies in drug development.
Raschi, E., Vasina, V., Poluzzi, E., & de Ponti, F. (2008) · Pharmacological Research · doi:10.1016/j.phrs.2008.01.009 · Cited by 144 · see citing works
“[23] Antzelevitch C, Pollevick GD, Cordeiro JM, Casis O, Sanguinetti MC,”
BackgroundBrugada syndrome: clinical and genetic findings
Sarquella-Brugada, G., Campuzano, Ó., Arbelo, E., Brugada, J., & Brugada, R. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.35 · Cited by 143 · see citing works
Berger, S., & Bartsch, D. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1936-3 · Cited by 143 · see citing works
Precision medicine and therapies of the future
Sisodiya, S. (2020) · Epilepsia · doi:10.1111/epi.16539 · Cited by 139 · see citing works
J Wave syndromes: Brugada and Early Repolarization Syndromes
Antzelevitch, C., & Yan, G.-X. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.04.014 · Cited by 139 · see citing works
Self-citationCardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances
Fernández-Falgueras, A., Sarquella‐Brugada, G., Brugada, J., Brugada, R., & Campuzano, Ó. (2017) · Biology · doi:10.3390/biology6010007 · Cited by 146 · see citing works
“5% of BrS cases in which patients present with a syndrome overlapping the typical BrS ECG pattern with a short QT interval [37,38].”
BackgroundDrug-induced Brugada syndrome.
Yap, Y., Behr, E., & Camm, A. (2009) · Europace · doi:10.1093/europace/eup114 · Cited by 135
“loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the a1- and b2b-subunits of the L-type calcium channel have been found to be the underlying cause.(5) Similarly, a mutation in the glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) gene has also been identified as a less commo…”
BackgroundIon Channel Macromolecular Complexes in Cardiomyocytes: Roles in Sudden Cardiac Death
Abriel, H., Rougier, J., & Jalife, J. (2015) · Circulation Research · doi:10.1161/circresaha.116.305017 · Cited by 133 · see citing works
“S481L) of the CACNB2 gene, encoding the Ca v β2 subunit, was found in a BrS patient.(71) Despite the large I Ca mutation-induced decrease in heterologous expression systems, no reduction of Ca V 1.”
BackgroundSzél, T., & Antzelevitch, C. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.01.067 · Cited by 133
“Discussion It is well established that mutations leading to a decrease in inward currents (INa or ICaL) or increase in outward currents (Ito and IK-ATP) are capable of causing BrS in humans (5,19-22).”
BackgroundSelf-citationGargus, J. J. (2008) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2008.03572.x · Cited by 131 · see citing works
Lu, H.-R., Vlaminckx, E., Hermans, A. N., Rohrbacher, J., van Ammel, K., Towart, R., Pugsley, M., & Gallacher, D. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.191 · Cited by 131 · see citing works
“, 2005) as well as ‘loss-of-function’ mutations in genes encoding the cardiac L-type calcium channel (Antzelevitch et al., 2007) have been associated to date with the congenital short QT syndrome.”
BackgroundKoncz, I., Gurabi, Z., Patocskai, B., Panama, B. K., Szél, T., Hu, D., Barajas-Martinez, H., & Antzelevitch, C. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.12.012 · Cited by 130 · see citing works
Self-citationCardiac channelopathies: Genetic and molecular mechanisms
Abriel, H., & Zaklyazminskaya, E. V. (2012) · Gene · doi:10.1016/j.gene.2012.12.061 · Cited by 118 · see citing works
Genetics of sudden death: focus on inherited channelopathies.
Cerrone, M., & Priori, S. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr082 · Cited by 128 · see citing works
Ohno, S., Zankov, D., Ding, W.-G., Itoh, H., Makiyama, T., Doi, T., Shizuta, S., Hattori, T., Miyamoto, A., Naiki, N., et al. (2011) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.110.959619 · Cited by 128 · see citing works
Defects in Ankyrin-Based Membrane Protein Targeting Pathways Underlie Atrial Fibrillation
Cunha, S. R., Hund, T. J., Hashemi, S., Voigt, N., Li, N., Wright, P., Koval, O. M., Li, J., Gudmundsson, H., Gumina, R. J., et al. (2011) · Circulation · doi:10.1161/circulationaha.111.023986 · Cited by 111 · see citing works
Myokit: A simple interface to cardiac cellular electrophysiology.
Clerx, M., Collins, P., Lange, E. D. D., & Volders, P. (2016) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2015.12.008 · Cited by 127 · see citing works
“A pathological case was created by reducing cell-to-cell conductance, decreasing gCaL to 50% (Antzelevitch et al., 2007), increasing epicardial and midmyocardial gTo to 250% and adding a shift in ITo voltage dependence.”
MethodQT-Interval Duration and Mortality Rate
Zhang, Y.-Y., Post, W., Dalal, D., Blasco-Colmenares, E., Tomaselli, G., & Guallar, E. (2011) · Archives of Internal Medicine · doi:10.1001/archinternmed.2011.433 · Cited by 126 · see citing works
Boczek, N. J., Best, J. M., Tester, D. J., Giudicessi, J. R., Middha, S., Evans, J. M., Kamp, T. J., & Ackerman, M. J. (2013) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.113.000138 · Cited by 111 · see citing works
Cordeiro, J., Marieb, M. A., Pfeiffer, R., Calloe, K., Burashnikov, E., & Antzelevitch, C. (2009) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.01.014 · Cited by 122 · see citing works
Self-citationAtrial fibrillation and Brugada syndrome.
Francis, J., & Antzelevitch, C. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.10.062 · Cited by 121 · see citing works
“Mutations in he and subunits of the calcium channel can also lead to shorter than normal QT interval, creating a new clinical ntity consisting of a combined Brugada/short-QT synrome (3).”
BackgroundInfluentialSelf-citationCalloe, K., Cordeiro, J., Diego, J. D. D., Hansen, R., Grunnet, M., Olesen, S., & Antzelevitch, C. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn339 · Cited by 120 · see citing works
“Our new experimental model of BrS also recapitulates the clinical finding that a slight increase in QT interval is observed in the right precordial leads in association with ST-segment elevation in some BrS patients.(6) Our model shows that the prolongation of APD90 in the epicardium is Figure 7 Effect of NS5806 to in…”
Self-citationHuman ether-a-go-go related gene (hERG) K+ channels: function and dysfunction.
Perrin, M., Subbiah, R., Vandenberg, J., & Hill, A. (2008) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2008.10.006 · Cited by 120 · see citing works
Channelopathy pathogenesis in autism spectrum disorders
Schmunk, G., & Gargus, J. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00222 · Cited by 118 · see citing works
“This is supported by the finding that the two missense alleles at this locus that cause the short QT Brugada syndrome, A39V and G490R, are loss-of-function lesions (Antzelevitch et al., 2007; Brugada et al., 2012).”
BackgroundBrugada Syndrome: Clinical, Genetic, Molecular, Cellular, and Ionic Aspects.
Antzelevitch, C., & Patocskai, B. (2016) · Current problems in cardiology · doi:10.1016/j.cpcardiol.2015.06.002 · Cited by 118 · see citing works
Self-citationCardiomyopathic and channelopathic causes of sudden unexplained death in infants and children.
Tester, D., & Ackerman, M. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.60.052907.103838 · Cited by 117 · see citing works
Structure and function of the β subunit of voltage-gated Ca2+ channels
Buraei, Z., & Yang, J. (2012) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamem.2012.08.028 · Cited by 114
Empiric quinidine therapy for asymptomatic Brugada syndrome: Time for a prospective registry
Viskin, S., Wilde, A., Tan, H. L., Antzelevitch, C., Shimizu, W., & Belhassen, B. (2008) · Heart Rhythm · doi:10.1016/j.hrthm.2008.11.030 · Cited by 114 · see citing works
Self-citationChahal, C., Salloum, M. N., Alahdab, F., Gottwald, J. A., Tester, D., Anwer, L. A., So, E. L., Murad, M., Louis, E. S. S., Ackerman, M., et al. (2019) · Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease · doi:10.1161/jaha.119.012264 · Cited by 109 · see citing works
“Likely deleterious variants in 373 genes were identified exclusively in the SUDEP group, 1 of which was CACNB2 associated with BrS (the exact variant is not reported and is predicted by in silico modeling only).(52,53) Other than the known SCN1A pathogenic variants in DS Figure 2.”
BackgroundFGF12 is a candidate Brugada syndrome locus
Hennessey, J. A., Marcou, C. A., Wang, C., Wei, E. Q., Wang, C.-J., Tester, D., Torchio, M., Dagradi, F., Crotti, L., Schwartz, P., et al. (2013) · Heart Rhythm · doi:10.1016/j.hrthm.2013.09.064 · Cited by 109 · see citing works
Benito, B., Guasch, E., Rivard, L., & Nattel, S. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.05.037 · Cited by 107 · see citing works
CaV1.2 channelopathies: from arrhythmias to autism, bipolar disorder, and immunodeficiency
Liao, P., & Soong, T. (2010) · Pflügers Archiv: European Journal of Physiology · doi:10.1007/s00424-009-0753-0 · Cited by 107 · see citing works
“2 channelopathy, a subsequent study of Brugada syndrome patients revealed a loss-of-function phenotype in either the pore-forming α1 subunit or the auxiliary β subunit [4].”
Modeling Short QT Syndrome Using Human‐Induced Pluripotent Stem Cell–Derived Cardiomyocytes
El-Battrawy, I., Lan, H., Cyganek, L., Zhao, Z.-H., Li, X., Buljubasic, F., Lang, S., Yücel, G., Sattler, K., Zimmermann, W., et al. (2018) · Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease · doi:10.1161/jaha.117.007394 · Cited by 105 · see citing works
“Additionally, overlap syndrome, SQTS with Brugada syndrome, has been reported.(12,13) Causes of acquired SQTS are electrolyte imbalance including hyperkalemia or hypercalcemia, myocardial ischemia, acidosis, or carnitine deficiency.”
BackgroundSelf-citation
- Authors
- Antzelevitch, C., Pollevick, G. D., Cordeiro, J. M., Casis, O., Sanguinetti, M. C., Aizawa, Y., Guerchicoff, A., Pfeiffer, R., Oliva, A., Wollnik, B., Gelber, P., Bonaros, E. P., Burashnikov, E., Wu, Y., Sargent, J. D., Schickel, S., Oberheiden, R., Bhatia, A., Hsu, L.-F., Haïssaguerre, M., Schimpf, R., Borggrefe, M., & Wolpert, C.
- Affiliations
- University of Cologne (DE)
- From the Masonic Medical Research Laboratory (C.A., G.D.P., J.M.C., H.A., A.G., R.P., A.O., E.B., Y.W.), Utica, NY; Nora Eccles Harrison Cardiovascular Research and Training Institute (O.C., M.C.S., J.D.S.), University of Utah, Salt Lake City, Utah; Center for Molecular Medicine Cologne (B.W.), Institute of Human Genetics, University of Cologne, Germany; Cardiovascular Consultants of Long Island (P.G., E.P.B.), New Hyde Park, NY; Department of Internal Medicine (S.S., R.O.), Academic Hospital...
- ORCID
- Venue
- Circulation
- Published
- 2007-01-30
- Volume
- 115
- Issue
- 4
- Pages
- 442-449
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC1952683
- OpenAlex
- W2089861793
- Cited by
- 933
- References
- 0
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 22 · 2023: 24 · 2022: 25 · 2021: 35 · 2020: 34 · 2019: 35 · 2018: 47 · 2017: 60 · 2016: 55 · 2015: 51 · 2014: 44 · 2013: 85 · 2012: 82
- FWCI
- 54.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- GRO (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL047678)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Keywords
- Brugada syndrome, L-type calcium channels, CACNA1C, CACNB2, CACNA2D1, loss-of-function mutations, sudden cardiac death, short QT interval, ST-segment elevation, cardiac ion channelopathy, channel trafficking, quinidine, ventricular tachycardia, familial arrhythmia
- MeSH terms
- Adult, Animals, Cricetulus, Electrocardiography, Family Health, Female, Cricetinae, Humans, Genetic Linkage, Male, Phenotype, Registries, Ventricular Fibrillation, Calcium Channels, Mutagenesis, Site-Directed, CHO Cells, Death, Sudden, Cardiac, Tachycardia, Ventricular, Patch-Clamp Techniques, Mutation, Missense, Calcium Channels, L-Type, White People
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