(Circulation. 1999;99:529-533.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Low Penetrance in the Long-QT Syndrome
Clinical Impact
From the Molecular Cardiology and Electrophysiology Laboratory, Fondazione "Salvatore Maugeri" IRCCS, Pavia (S.G.P., C.N.); the Department of Cardiology, University of Pavia and Policlinico S. Matteo IRCCS, Pavia (P.J.S.); and the Centro di Fisiologia Clinica e Ipertensione, University of Milan, Ospedale Maggiore IRCCS, Milan (C.N.), Italy.
Correspondence to Silvia G. Priori, MD, PhD, Molecular Cardiology and Electrophysiology Laboratory, Fondazione "S. Maugeri" IRCCS, Via Ferrata, 8, 27100 Pavia, Italy. E-mail spriori{at}fsm.it
Background—It is still currently held that most patients affected by the long-QT syndrome (LQTS) show QT interval prolongation or clinical symptoms. This is reflected by the assumption in linkage studies of a penetrance of 90%. We had previously suggested that a larger-than-anticipated number of LQTS patients might be affected without showing clinical signs. We have now exploited the availability of molecular diagnosis to test this hypothesis.
Methods and Results—We identified 9 families with "sporadic" cases of LQTS, ie, families in which, besides the proband, none of the family members had clinical signs of the disease. Mutation screening by conventional single-strand conformational polymorphism and sequencing was performed on DNA of probands and family members to identify mutation carriers. Of 46 family members considered on clinical grounds to be nonaffected, 15 (33%) were found instead to be gene carriers. Penetrance was found to be 25%. In these families, conventional clinical diagnostic criteria had a sensitivity of only 38% in correctly identifying carriers of the genetic defect.
Conclusions—This study demonstrates that in some families, LQTS may appear with a very low penetrance, a finding with multiple clinical implications. The family members considered to be normal and found to be silent gene carriers are unexpectedly at risk of generating affected offspring and also of developing torsade de pointes if exposed to either cardiac or noncardiac drugs that block potassium channels. It is no longer acceptable to exclude LQTS among family members of definitely affected patients on purely clinical grounds. Conversely, it now appears appropriate to perform molecular screening in all family members of genotyped patients.
Key Words: arrhythmia • genetics • molecular biology • torsade de pointes • sudden death
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|
|
|
|
|
|
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|
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|
|
|
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|
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|
|
 |
|
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|
|
|
|
|
|
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|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 S. Poelzing, B. J. Roth, and D. S. Rosenbaum Optical measurements reveal nature of intercellular coupling across ventricular wall Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1428 - H1435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Crotti, A. L. Lundquist, R. Insolia, M. Pedrazzini, C. Ferrandi, G. M. De Ferrari, A. Vicentini, P. Yang, D. M. Roden, A. L. George Jr, et al. KCNH2-K897T Is a Genetic Modifier of Latent Congenital Long-QT Syndrome Circulation, August 30, 2005; 112(9): 1251 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R Shah Pharmacogenetics in drug regulation: promise, potential and pitfalls Phil Trans R Soc B, August 29, 2005; 360(1460): 1617 - 1638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Bezzina, A. A.M. Wilde, and D. M. Roden The molecular genetics of arrhythmias Cardiovasc Res, August 15, 2005; 67(3): 343 - 346. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 T Rossenbacker, E Schollen, C Kuiperi, T J L de Ravel, K Devriendt, G Matthijs, D Collen, H Heidbuchel, and P Carmeliet Unconventional intronic splice site mutation in SCN5A associates with cardiac sodium channelopathy J. Med. Genet., May 1, 2005; 42(5): e29 - e29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bellocq, R. Wilders, J.-J. Schott, B. Louerat-Oriou, P. Boisseau, H. Le Marec, D. Escande, and I. Baro A Common Antitussive Drug, Clobutinol, Precipitates the Long QT Syndrome 2 Mol. Pharmacol., November 1, 2004; 66(5): 1093 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Choi, L. J. Kopplin, D. J. Tester, M. L. Will, C. M. Haglund, and M. J. Ackerman Spectrum and Frequency of Cardiac Channel Defects in Swimming-Triggered Arrhythmia Syndromes Circulation, October 12, 2004; 110(15): 2119 - 2124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, G. M. Vincent, M. Baralle, F. E. Baralle, B. D. Anson, D. W. Benson, B. Whiting, K. W. Timothy, J. Carlquist, C. T. January, et al. An intronic mutation causes long QT syndrome J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1283 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Shimizu, M. Horie, S. Ohno, K. Takenaka, M. Yamaguchi, M. Shimizu, T. Washizuka, Y. Aizawa, K. Nakamura, T. Ohe, et al. Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: Multicenter study in Japan J. Am. Coll. Cardiol., July 7, 2004; 44(1): 117 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gouas, C. Bellocq, M. Berthet, F. Potet, S. Demolombe, A. Forhan, R. Lescasse, F. Simon, B. Balkau, I. Denjoy, et al. New KCNQ1 mutations leading to haploinsufficiency in a general population: Defective trafficking of a KvLQT1 mutant Cardiovasc Res, July 1, 2004; 63(1): 60 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Schwartz Stillbirths, Sudden Infant Deaths, and Long-QT Syndrome: Puzzle or Mosaic, the Pieces of the Jigsaw Are Being Fitted Together Circulation, June 22, 2004; 109(24): 2930 - 2932. [Full Text] [PDF]
|
|
|
|
|
|
B. J. Maron, B. R. Chaitman, M. J. Ackerman, A. Bayes de Luna, D. Corrado, J. E. Crosson, B. J. Deal, D. J. Driscoll, N.A. M. Estes III, C. G. S. Araujo, et al. Recommendations for Physical Activity and Recreational Sports Participation for Young Patients With Genetic Cardiovascular Diseases Circulation, June 8, 2004; 109(22): 2807 - 2816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rosati and D. McKinnon Regulation of Ion Channel Expression Circ. Res., April 16, 2004; 94(7): 874 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Roden Drug-Induced Prolongation of the QT Interval N. Engl. J. Med., March 4, 2004; 350(10): 1013 - 1022. [Full Text] [PDF]
|
|
|
|
|
|
S. G. Priori Inherited Arrhythmogenic Diseases: The Complexity Beyond Monogenic Disorders Circ. Res., February 6, 2004; 94(2): 140 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Shafer, A. S. Habib, and T. J. Gan Safety of Patients Reason for FDA Black Box Warning on Droperidol * Response Anesth. Analg., February 1, 2004; 98(2): 551 - 552. [Full Text] [PDF]
|
|
|
|
|
|
C. Napolitano Transgenic models in cardiac arrhythmias: how close can we get to the bedside? Cardiovasc Res, February 1, 2004; 61(2): 206 - 207. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Anantharam, S. M. Markowitz, and G. W. Abbott Pharmacogenetic Considerations in Diseases of Cardiac Ion Channels J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 831 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Beery, M. Dyment, K. Shooner, T. K. Knilans, and D. W. Benson A Candidate Locus Approach Identifies a Long QT Syndrome Gene Mutation Biol Res Nurs, October 1, 2003; 5(2): 97 - 104. [Abstract] [PDF]
|
|
|
|
|
|
W. Zareba, A. J. Moss, E. H. Locati, M. H. Lehmann, D. R. Peterson, W. J. Hall, P. J. Schwartz, G. M. Vincent, S. G. Priori, J. Benhorin, et al. Modulating effects of age and gender on the clinical course of long QT syndrome by genotype J. Am. Coll. Cardiol., July 2, 2003; 42(1): 103 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Bezzina, A. O. Verkerk, A. Busjahn, A. Jeron, J. Erdmann, T. T. Koopmann, Z. A. Bhuiyan, R. Wilders, M. M.A.M. Mannens, H. L. Tan, et al. A common polymorphism in KCNH2 (HERG) hastens cardiac repolarization Cardiovasc Res, July 1, 2003; 59(1): 27 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Priori, P. J. Schwartz, C. Napolitano, R. Bloise, E. Ronchetti, M. Grillo, A. Vicentini, C. Spazzolini, J. Nastoli, G. Bottelli, et al. Risk Stratification in the Long-QT Syndrome N. Engl. J. Med., May 8, 2003; 348(19): 1866 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Al-Khatib, N. M. A. LaPointe, J. M. Kramer, and R. M. Califf What Clinicians Should Know About the QT Interval JAMA, April 23, 2003; 289(16): 2120 - 2127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Firoozi, E Behr, and W McKenna Elite athletes with recurrent ERS Eur. Heart J., April 2, 2003; 24(8): 783 - 783. [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Lees-Miller, J. Guo, J. R. Somers, D. E. Roach, R. S. Sheldon, D. E. Rancourt, and H. J. Duff Selective Knockout of Mouse ERG1 B Potassium Channel Eliminates IKr in Adult Ventricular Myocytes and Elicits Episodes of Abrupt Sinus Bradycardia Mol. Cell. Biol., March 15, 2003; 23(6): 1856 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Shimizu, T. Noda, H. Takaki, T. Kurita, N. Nagaya, K. Satomi, K. Suyama, N. Aihara, S. Kamakura, K. Sunagawa, et al. Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome J. Am. Coll. Cardiol., February 19, 2003; 41(4): 633 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I M Van Langen, E Birnie, M Alders, R J Jongbloed, H Le Marec, and A A M Wilde The use of genotype-phenotype correlations in mutation analysis for the long QT syndrome J. Med. Genet., February 1, 2003; 40(2): 141 - 145. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Pereon, G. Lande, S. Demolombe, S. Nguyen The Tich, D. Sternberg, H. Le Marec, and A. David Paramyotonia congenita with an SCN4A mutation affecting cardiac repolarization Neurology, January 28, 2003; 60(2): 340 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Firouzi and W. A. Groenewegen Gene polymorphisms and cardiac arrhythmias Europace, January 1, 2003; 5(3): 235 - 242. [Full Text] [PDF]
|
|
|
|
 |
|
 X. H.T. Wehrens, M. A. Vos, P. A. Doevendans, and H. J.J. Wellens Novel Insights in the Congenital Long QT Syndrome Ann Intern Med, December 17, 2002; 137(12): 981 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Makita, M. Horie, T. Nakamura, T. Ai, K. Sasaki, H. Yokoi, M. Sakurai, I. Sakuma, H. Otani, H. Sawa, et al. Drug-Induced Long-QT Syndrome Associated With a Subclinical SCN5A Mutation Circulation, September 3, 2002; 106(10): 1269 - 1274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.J. Schwartz, A. Garson Jr, T. Paul, M. Stramba-Badiale, V.L. Vetter, E. Villain, and C. Wren Guidelines for the interpretation of the neonatal electrocardiogram Eur. Heart J., September 1, 2002; 23(17): 1329 - 1344. [Full Text] [PDF]
|
|
|
|
|
|
D. M. Roden The problem, challenge and opportunity of genetic heterogeneity in monogenic diseases predisposing to sudden death J. Am. Coll. Cardiol., July 17, 2002; 40(2): 357 - 359. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
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 J. C. Perry Inferring Long QT1 Genotype Based on a Simple Epinephrine Infusion Protocol: From the Bedside to the Bench and Back Mayo Clin. Proc., May 1, 2002; 77(5): 405 - 406. [PDF]
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M. J. Ackerman, A. Khositseth, D. J. Tester, J. B. Hejlik, W.-K. Shen, and C.-b. J. Porter Epinephrine-Induced QT Interval Prolongation: A Gene-Specific Paradoxical Response in Congenital Long QT Syndrome Mayo Clin. Proc., May 1, 2002; 77(5): 413 - 421. [Abstract] [PDF]
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 M Malik, P Farbom, V Batchvarov, K Hnatkova, and A J Camm Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval Heart, March 1, 2002; 87(3): 220 - 228. [Abstract] [Full Text] [PDF]
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Members of the Sicilian Gambit New Approaches to Antiarrhythmic Therapy, Part I: Emerging Therapeutic Applications of the Cell Biology of Cardiac Arrhythmias Circulation, December 4, 2001; 104(23): 2865 - 2873. [Abstract] [Full Text] [PDF]
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Members of the Sicilian Gambit New approaches to antiarrhythmic therapy; emerging therapeutic applications of the cell biology of cardiac arrhythmias Eur. Heart J., December 1, 2001; 22(23): 2148 - 2163. [Abstract] [PDF]
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Members of the Sicilian Gambit New approaches to antiarrhythmic therapy: emerging therapeutic applications of the cell biology of cardiac arrhythmias Cardiovasc Res, December 1, 2001; 52(3): 345 - 360. [Abstract] [Full Text] [PDF]
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 D. Escande Inhibition of repolarizing ionic currents by drugs Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K17 - K22. [Abstract] [PDF]
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E. Schulze-Bahr, W. Haverkamp, L. Eckardt, P. Kirchhof, H. Wedekind, and G. Breithardt Genetic aspects in acquired long QT syndrome -- a piece in the puzzle Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K48 - K52. [Abstract] [PDF]
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L. Huang, M. Bitner-Glindzicz, L. Tranebjaerg, and A. Tinker A spectrum of functional effects for disease causing mutations in the Jervell and Lange-Nielsen syndrome Cardiovasc Res, September 1, 2001; 51(4): 670 - 680. [Abstract] [Full Text] [PDF]
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S.G. Priori, E. Aliot, C. Blomstrom-Lundqvist, L. Bossaert, G. Breithardt, P. Brugada, A.J. Camm, R. Cappato, S.M. Cobbe, C. Di Mario, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology Eur. Heart J., August 2, 2001; 22(16): 1374 - 1450. [PDF]
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 L. A. Larsen, P. S. Andersen, J. Kanters, I. H. Svendsen, J. R. Jacobsen, J. Vuust, G. Wettrell, L. Tranebjarg, J. Bathen, and M. Christiansen Screening for Mutations and Polymorphisms in the Genes KCNH2 and KCNE2 Encoding the Cardiac HERG/MiRP1 Ion Channel: Implications for Acquired and Congenital Long Q-T Syndrome Clin. Chem., August 1, 2001; 47(8): 1390 - 1395. [Abstract] [Full Text] [PDF]
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J. Kimbrough, A. J. Moss, W. Zareba, J. L. Robinson, W. J. Hall, J. Benhorin, E. H. Locati, A. Medina, C. Napolitano, S. Priori, et al. Clinical Implications for Affected Parents and Siblings of Probands With Long-QT Syndrome Circulation, July 31, 2001; 104(5): 557 - 562. [Abstract] [Full Text] [PDF]
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P. M. Spooner, C. Albert, E. J. Benjamin, R. Boineau, R. C. Elston, A. L. George Jr, X. Jouven, L. H. Kuller, J. W. MacCluer, E. Marban, et al. Sudden Cardiac Death, Genes, and Arrhythmogenesis : Consideration of New Population and Mechanistic Approaches From a National Heart, Lung, and Blood Institute Workshop, Part I Circulation, May 15, 2001; 103(19): 2361 - 2364. [Abstract] [Full Text] [PDF]
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S. G Priori, C. Napolitano, and M. Grillo Concealed arrhythmogenic syndromes: the hidden substrate of idiopathic ventricular fibrillation? Cardiovasc Res, May 1, 2001; 50(2): 218 - 223. [Abstract] [Full Text] [PDF]
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G. Lande, S. Demolombe, A. Bammert, A. Moorman, F. Charpentier, and D. Escande Transgenic mice overexpressing human KvLQT1 dominant-negative isoform Part II: Pharmacological profile Cardiovasc Res, May 1, 2001; 50(2): 328 - 334. [Abstract] [Full Text] [PDF]
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P. Chevalier, C. Rodriguez, L. Bontemps, M. Miquel, G. Kirkorian, R. Rousson, F. Potet, J.-J. Schott, I. Baro, and P. Touboul Non-invasive testing of acquired long QT syndrome: Evidence for multiple arrhythmogenic substrates Cardiovasc Res, May 1, 2001; 50(2): 386 - 398. [Abstract] [Full Text] [PDF]
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 J. A. Towbin, Z. Wang, and H. Li Genotype and Severity of Long QT Syndrome Drug Metab. Dispos., April 1, 2001; 29(4): 574 - 579. [Abstract] [Full Text]
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G. Lande, F. Kyndt, I. Baro, D. Chabannes, P. Boisseau, J.-C. Pony, D. Escande, and H. Le Marec Dynamic analysis of the QT interval in long QT1 syndrome patients with a normal phenotype Eur. Heart J., March 1, 2001; 22(5): 410 - 422. [Abstract] [PDF]
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C. R Bezzina, M. B Rook, and A. A.M Wilde Cardiac sodium channel and inherited arrhythmia syndromes Cardiovasc Res, February 1, 2001; 49(2): 257 - 271. [Full Text] [PDF]
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S. G. Priori, C. Napolitano, N. Tiso, M. Memmi, G. Vignati, R. Bloise, V. Sorrentino, and G. A. Danieli Mutations in the Cardiac Ryanodine Receptor Gene (hRyR2) Underlie Catecholaminergic Polymorphic Ventricular Tachycardia Circulation, January 16, 2001; 103(2): 196 - 200. [Abstract] [Full Text] [PDF]
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S. G. Priori, R. Bloise, and L. Crotti The long QT syndrome Europace, January 1, 2001; 3(1): 16 - 27. [PDF]
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A. A. M. Wilde and D. M. Roden Predicting the Long-QT Genotype From Clinical Data : From Sense to Science Circulation, December 5, 2000; 102(23): 2796 - 2798. [Full Text] [PDF]
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