Published online before print September 26, 2002, doi: 10.1161/01.RES.0000038886.18992.6B
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
UltraRapid Communication |
Absence of Calsequestrin 2 Causes Severe Forms of Catecholaminergic Polymorphic Ventricular Tachycardia
From INSERM U523 (A.V.P., I.D., J.-M.L., P.G.), Institut de Myologie, IFR "C
ur, muscles et vaisseaux" No. 14, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; the Experimental and Molecular Cardiology Group (A.V.P., A.A.M.W.), Academic Medical Center, Amsterdam, the Netherlands; Service de Cardiologie (I.D.), Hôpital Lariboisière-Paris, Paris, France; the Paediatric Department (T.M.H.), Antonius Ziekenhuis, Nieuwegein, the Netherlands; Service de Cardiologie Pédiatrique (J.-M.L.), Hôpital Robert Debré-Paris, Paris, France; Service de Cardiologie (A.D.C.), Hôpital Nord, St-Etienne, France; Laboratoire de Génétique et Insuffisance Cardiaque (P.S.), Association Claude Bernard, IFR 14, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; and the Department of Clinical Genetics (M.M.A.M.M.), Academic Medical Center, Amsterdam, the Netherlands.
Correspondence to Pascale Guicheney, INSERM U 523, Groupe Hospitalier Pitié-Salpêtrière, 47 boulevard de l’Hôpital, 75651 Paris cedex 13, France. E-mail p.guicheney{at}myologie.chups.jussieu.fr
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmogenic disorder characterized by syncopal events and sudden cardiac death at a young age during physical stress or emotion, in the absence of structural heart disease. We report the first nonsense mutations in the cardiac calsequestrin gene, CASQ2, in three CPVT families. The three mutations, a nonsense R33X, a splicing 532+1 G>A, and a 1-bp deletion, 62delA, are thought to induce premature stop codons. Two patients who experienced syncopes before the age of 7 years were homozygous carriers, suggesting a complete absence of calsequestrin 2. One patient was heterozygous for the stop codon and experienced syncopes from the age of 11 years. Despite the different mutations, there is little phenotypic variation of CPVT for the CASQ2 mutations. Of the 16 heterozygous carriers of these various mutations, 14 were devoid of clinical symptoms or ECG anomalies, whereas 2 of them had ventricular arrhythmias at ECG on exercise tests. In line with this, the diagnosis of the probands was difficult because of the absence of a positive family history. In conclusion, these additional three CASQ2 CPVT families suggest that CASQ2 mutations are more common than previously thought and produce a severe form of CPVT. The full text of this article is available at http://www.circresaha.org.
Key Words: calsequestrin • tachycardia • syncope • arrhythmia • genetics
This article has been cited by other articles:
 |
|
 |
|
  N. Liu and S. G. Priori Disruption of calcium homeostasis and arrhythmogenesis induced by mutations in the cardiac ryanodine receptor and calsequestrin Cardiovasc Res, January 15, 2008; 77(2): 293 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. George Sarcoplasmic reticulum Ca2+ leak in heart failure: mere observation or functional relevance? Cardiovasc Res, January 15, 2008; 77(2): 302 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gyorke and D. Terentyev Modulation of ryanodine receptor by luminal calcium and accessory proteins in health and cardiac disease Cardiovasc Res, January 15, 2008; 77(2): 245 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Reyes-Juarez, R. Juarez-Rubi, G. Rodriguez, and A. Zarain-Herzberg Transcriptional Analysis of the Human Cardiac Calsequestrin Gene in Cardiac and Skeletal Myocytes J. Biol. Chem., December 7, 2007; 282(49): 35554 - 35563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. A. Bhuiyan, M. P. van den Berg, J. P. van Tintelen, M. T.E. Bink-Boelkens, A. C.P. Wiesfeld, M. Alders, A. V. Postma, I. van Langen, M. M.A.M. Mannens, and A. A.M. Wilde Expanding Spectrum of Human RYR2-Related Disease: New Electrocardiographic, Structural, and Genetic Features Circulation, October 2, 2007; 116(14): 1569 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Antzelevitch Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2024 - H2038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. H. Robin, P. B. Tabereaux, R. Benza, and B. R. Korf Genetic Testing in Cardiovascular Disease J. Am. Coll. Cardiol., August 21, 2007; 50(8): 727 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Gergs, T. Berndt, J. Buskase, L. R. Jones, U. Kirchhefer, F. U. Muller, K.-D. Schluter, W. Schmitz, and J. Neumann On the role of junctin in cardiac Ca2+ handling, contractility, and heart failure Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H728 - H734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Yuan, G.-C. Fan, M. Dong, B. Altschafl, A. Diwan, X. Ren, H. H. Hahn, W. Zhao, J. R. Waggoner, L. R. Jones, et al. Sarcoplasmic Reticulum Calcium Overloading in Junctin Deficiency Enhances Cardiac Contractility but Increases Ventricular Automaticity Circulation, January 23, 2007; 115(3): 300 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Hove-Madsen, C. Prat-Vidal, A. Llach, F. Ciruela, V. Casado, C. Lluis, A. Bayes-Genis, J. Cinca, and R. Franco Adenosine A2A receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release Cardiovasc Res, November 1, 2006; 72(2): 292 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. di Barletta, S. Viatchenko-Karpinski, A. Nori, M. Memmi, D. Terentyev, F. Turcato, G. Valle, N. Rizzi, C. Napolitano, S. Gyorke, et al. Clinical Phenotype and Functional Characterization of CASQ2 Mutations Associated With Catecholaminergic Polymorphic Ventricular Tachycardia Circulation, September 5, 2006; 114(10): 1012 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Milting, N. Lukas, B. Klauke, R. Korfer, A. Perrot, K.-J. Osterziel, J. Vogt, S. Peters, R. Thieleczek, and M. Varsanyi Composite polymorphisms in the ryanodine receptor 2 gene associated with arrhythmogenic right ventricular cardiomyopathy Cardiovasc Res, August 1, 2006; 71(3): 496 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, L. Xu, H. Duan, D. A. Pasek, J. P. Eu, and G. Meissner Knocking Down Type 2 but Not Type 1 Calsequestrin Reduces Calcium Sequestration and Release in C2C12 Skeletal Muscle Myotubes J. Biol. Chem., June 2, 2006; 281(22): 15572 - 15581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A V Postma, I Denjoy, J Kamblock, M Alders, J-M Lupoglazoff, G Vaksmann, L Dubosq-Bidot, P Sebillon, M M A M Mannens, P Guicheney, et al. Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients J. Med. Genet., November 1, 2005; 42(11): 863 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaab and E. Schulze-Bahr Susceptibility genes and modifiers for cardiac arrhythmias Cardiovasc Res, August 15, 2005; 67(3): 397 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Milan and C. A. MacRae Animal models for arrhythmias Cardiovasc Res, August 15, 2005; 67(3): 426 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-B. Nam, A. Burashnikov, and C. Antzelevitch Cellular Mechanisms Underlying the Development of Catecholaminergic Ventricular Tachycardia Circulation, May 31, 2005; 111(21): 2727 - 2733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Tavi, A. Hansson, S.-J. Zhang, N.-G. Larsson, and H. Westerblad Abnormal Ca2+ release and catecholamine-induced arrhythmias in mitochondrial cardiomyopathy Hum. Mol. Genet., April 15, 2005; 14(8): 1069 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Antzelevitch Cardiac repolarization. The long and short of it Europace, January 1, 2005; 7(s2): S3 - S9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Jiang, B. Xiao, D. Yang, R. Wang, P. Choi, L. Zhang, H. Cheng, and S. R. W. Chen RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca2+ release (SOICR) PNAS, August 31, 2004; 101(35): 13062 - 13067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Terentyev, S. Viatchenko-Karpinski, I. Gyorke, P. Volpe, S. C. Williams, and S. Gyorke Calsequestrin determines the functional size and stability of cardiac intracellular calcium stores: Mechanism for hereditary arrhythmia PNAS, September 30, 2003; 100(20): 11759 - 11764. [Abstract] [Full Text] [PDF]
|
|