Genetic testing for potentially lethal, highly treatable inherited cardiomyopathies/channelopathies in clinical practice

Circulation

Volumn 123, Issue 9, 2011, Pages 1021-1037

  Tester, David J ^a   Ackerman, Michael J ^a,b  

^a Windland Smith Rice Sudden Death Genomics Laboratory   (United States)

^b MAYO CLINIC   (United States)

Author keywords

arrhythmia; cardiomyopathy; genetic testing; genetics; ion channels; long QT syndrome

Indexed keywords

ARTICLE; BRUGADA SYNDROME; CARDIAC CHANNELOPATHY; CARDIOMYOPATHY; CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA; CLINICAL PRACTICE; CONGESTIVE CARDIOMYOPATHY; GENE FREQUENCY; GENE LOCUS; GENETIC COUNSELING; GENETIC SCREENING; GENETIC VARIABILITY; GENOTYPE; HEART RIGHT VENTRICLE DYSPLASIA; HUMAN; HYPERTROPHIC CARDIOMYOPATHY; INDEL MUTATION; LONG QT SYNDROME; MISSENSE MUTATION; PRIORITY JOURNAL;

ANIMALS; CARDIOMYOPATHIES; CHANNELOPATHIES; GENE THERAPY; GENETIC TESTING; GENETIC VARIATION; HUMANS; MUTATION; TREATMENT OUTCOME;

EID: 79952715853     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.109.914838     Document Type: Article

References (79)

1. Nussbaum RL, McInnes RR, Willard HF. Thompson & Thompson Genetics in Medicine. 6th ed. Philadelphia, PA: WB Saunders; 2001: 51-94.
2. Den Dunnen JT, Antonarakis SE. Nomenclature for the description of human sequence variations. Hum Genet. 2001;109:121-124. (Pubitemid 32743202)
3. Tester DJ, Will ML, Haglund CM, Ackerman MJ. Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005;2:507-517. (Pubitemid 40521365)
4. Tester DJ, Ackerman MJ. Genetic testing. In: Wilde AAM, Friedman PA, Ackerman MJ, Shen W-K, Gussak I, Antzelevitch C, eds. Electrical Diseases of the Heart: Genetics, Mechanisms, Treatment, Prevention. London, UK: Springer; 2008:444-458.
5. Miller TE, Estrella E, Myerburg RJ, Garcia de Viera J, Moreno N, Rusconi P, Ahearn ME, Baumbach L, Kurlansky P, Wolff G, Bishopric NH. Recurrent third-trimester fetal loss and maternal mosaicism for long-QT syndrome. Circulation. 2004;109:3029-3034. (Pubitemid 38808326)
6. Gladding PA, Evans CA, Crawford J, Chung SK, Vaughan A, Webster D, Neas K, Love DR, Rees MI, Shelling AN, Skinner Jr. Posthumous diagnosis of long QT syndrome from neonatal screening cards. Heart Rhythm. 2010;7:481-486.
7. Tester DJ, Ackerman MJ. The role of molecular autopsy in unexplained sudden cardiac death. Curr Opin Cardiol. 2006;21:166-172. (Pubitemid 44315078)
8. Carturan E, Tester DJ, Brost BC, Basso C, Thiene G, Ackerman MJ. Postmortem genetic testing for conventional autopsy-negative sudden unexplained death: an evaluation of different DNA extraction protocols and the feasibility of mutational analysis from archival paraffinembedded heart tissue. Am J Clin Pathol. 2008;129:391-397. (Pubitemid 352029291)
9. Tester DJ, Cronk LB, Carr JL, Schulz V, Salisbury BA, Judson RS, Ackerman MJ. Allelic dropout in long QT syndrome genetic testing: a possible mechanism underlying false-negative results. Heart Rhythm. 2006;3:815-821. (Pubitemid 43982125)
10. Tester DJ, Will ML, Ackerman MJ. Mutation detection in congenital long QT syndrome: cardiac channel gene screen using PCR, dHPLC, and direct DNA sequencing. Methods Mol Med. 2006;128:181-207.
11. Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet. 2008;9:387-402.
12. Porreca GJ, Zhang K, Li JB, Xie B, Austin D, Vassallo SL, LeProust EM, Peck BJ, Emig CJ, Dahl F, Gao Y, Church GM, Shendure J. Multiplex amplification of large sets of human exons. Nat Methods. 2007;4: 931-936. (Pubitemid 350042382)
13. Eddy C-A, MacCormick JM, Chung S-K, Crawford JR, Love DR, Rees MI, Skinner JR, Shelling AN. Identification of large gene deletions and duplications in KCNQ1 and KCNH2 in patients with long QT syndrome. Heart Rhythm. 2008;5:1275-1281.
14. Koopmann TT, Alders M, Jongbloed RJ, Guerrero S, Mannens MMAM, Wilde AAM, Bezzina CR. Long QT syndrome caused by a large duplication in the KCNH2 (HERG) gene undetectable by current polymerase chain reaction-based exon-scanning methodologies. Heart Rhythm. 2006;3:52-55. (Pubitemid 43071890)
15. Tester DJ, Ackerman MJ. Novel gene and mutation discovery in congenital long QT syndrome: let's keep looking where the street lamp standeth. Heart Rhythm. 2008;5:1282-1284.
16. Constantin CM, Faucett A, Lubin IM. A primer on genetic testing. J Midwifery Womens Health. 2005;50:197-204. (Pubitemid 40645365)
17. Ehrmeyer SS, Laessig RH. Regulatory compliance for point-of-care testing: 2009 United States perspective. Clin Lab Med. 2009;29:463-478.
18. Maron BJ, Moller JH, Seidman CE, Vincent GM, Dietz HC, Moss AJ, Towbin JA, Sondheimer HM, Pyeritz RE, McGee G, Epstein AE. Impact of laboratory molecular diagnosis on contemporary diagnostic criteria for genetically transmitted cardiovascular diseases: hypertrophic cardiomyopathy, long-QT syndrome, and Marfan syndrome: a statement for healthcare professionals from the Councils on Clinical Cardiology, Cardiovascular Disease in the Young, and Basic Science, American Heart Association. Circulation. 1998;98:1460-1471. (Pubitemid 28463515)
19. Blue Cross and Blue Shield Association. Technology Evaluation Center report. Genetic Testing for Long QT Syndrome. Assessment Program. Volume 22, No. 9. February 2008. Available at: http://www.bcbsm.com/ mprApp/ MedicalPolicyDocument?fileId-2006787. Accessed February 4, 2011.
20. GeneTests: Medical Genetics Information Resource [database online]. Seattle, WA: University of Washington 1993-2009. Available at: http:// www.genetests.org. Accessed June 1, 2010.
21. Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol. 2009;54:201-211.
22. Shimizu W. Clinical impact of genetic studies in lethal inherited cardiac arrhythmias. Circ J. 2008;72:1926-1936.
23. Ruan Y, Liu N, Napolitano C, Priori SG. Therapeutic strategies for long-QT syndrome: does the molecular substrate matter? Circ Arrhythm Electrophysiol. 2008;1:290-297.
24. Tester DJ, Ackerman MJ. Genetic testing for cardiac channelopathies: ten questions regarding clinical considerations for heart rhythm allied professionals. Heart Rhythm. 2005;2:675-677. (Pubitemid 40724141)
25. Priori SG, Napolitano C. Role of genetic analyses in cardiology: part I: mendelian diseases: cardiac channelopathies. Circulation. 2006;113: 1130-1135.
26. Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, Wilde AAM, Ackerman MJ. Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009;120:1752-1760.
27. Charron P. Clinical genetics in cardiology. Heart. 2006;92:1172-1176.
28. Hershberger RE, Cowan J, Morales A, Siegfried JD. Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Heart Fail. 2009;2:253-261.
29. Van Riper M. Genetic testing and the family. J Midwifery Womens Health. 2005;50:227-233. (Pubitemid 40645369)
30. Thomas SM. Society and ethics: the genetics of disease. Curr Opin Genet Dev. 2004;14:287-291.
31. Lea DH, Williams J, Donahue MP. Ethical issues in genetic testing. J Midwifery Womens Health. 2005;50:234-240. (Pubitemid 40645370)
32. Abiola S. Recent developments in health law: the Genetic Information Nondiscrimination Act of 2008: "First major Civil Rights bill of the century" bars misuse of genetic test results. J Law Med Ethics. 2008;36:856-860.
33. Bos JM, Ommen SR, Ackerman MJ. Genetics of hypertrophic cardiomyopathy: one, two, or more diseases? Curr Opin Cardiol. 2007;22: 193-199. (Pubitemid 46581194)
34. Hershberger RE, Lindenfeld J, Mestroni L, Seidman CE, Taylor MRG, Towbin JA, Heart Failure Society of A. Genetic evaluation of cardiomyopathy: a Heart Failure Society of America practice guideline. J Card Fail. 2009;15:83-97.
35. Robin NH, Tabereaux PB, Benza R, Korf BR. Genetic testing in cardiovascular disease. J Am Coll Cardiol. 2007;50:727-737. (Pubitemid 47239314)
36. Marian AJ, Roberts R. The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2001;33:655-670. (Pubitemid 32538979)
37. Van Driest SL, Ommen SR, Tajik AJ, Gersh BJ, Ackerman MJ. Sarcomeric genotyping in hypertrophic cardiomyopathy. Mayo Clin Proc. 2005;80:463-469. (Pubitemid 40471377)
38. Binder J, Ommen SR, Gersh BJ, Van Driest SL, Tajik AJ, Nishimura RA, Ackerman MJ. Echocardiography-guided genetic testing in hypertrophic cardiomyopathy: septal morphological features predict the presence of myofilament mutations. Mayo Clin Proc. 2006;81:459-467.
39. Semsarian C, Ahmad I, Giewat M, Georgakopoulos D, Schmitt JP, McConnell BK, Reiken S, Mende U, Marks AR, Kass DA, Seidman CE, Seidman JG. The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. J Clin Invest. 2002;109:1013-1020. (Pubitemid 34408576)
40. Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, Seidman JG. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med. 1992;326:1108-1114.
41. Ackerman MJ, Van Driest SV, Ommen SR, Will ML, Nishimura RA, Tajik AJ, Gersh BJ. Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T gene in hypertrophic cardiomyopathy: a comprehensive outpatient perspective. J Am Coll Cardiol. 2002;39:2042-2048. (Pubitemid 34628288)
42. Van Driest SV, Ackerman MJ, Ommen SR, Shakur R, Will ML, Nishimura RA, Tajik AJ, Gersh BJ. Prevalence and severity of "benign" mutations in the beta myosin heavy chain, cardiac troponin-T, and alpha tropomyosin genes in hypertrophic cardiomyopathy. Circulation. 2002; 106:3085-3090. (Pubitemid 35440293)
43. Van Driest SL, Ommen SR, Tajik AJ, Gersh BJ, Ackerman MJ. Yield of genetic testing in hypertrophic cardiomyopathy. Mayo Clin Proc. 2005; 80:739-744. (Pubitemid 40770360)
44. Olivotto I, Girolami F, Ackerman MJ, Nistri S, Bos JM, Zachara E, Ommen SR, Theis JL, Vaubel RA, Re F, Armentano C, Poggesi C, Torricelli F, Cecchi F. Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. Mayo Clin Proc. 2008;83:630-638. (Pubitemid 351810562)
45. Schwartz PJ, Stramba-Badiale M, Crotti L, Pedrazzini M, Besana A, Bosi G, Gabbarini F, Goulene K, Insolia R, Mannarino S, Mosca F, Nespoli L, Rimini A, Rosati E, Salice P, Spazzolini C. Prevalence of the congenital long-QT syndrome. Circulation. 2009;120:1761-1767.
46. Tester DJ, Ackerman MJ. Postmortem long QT syndrome genetic testing for sudden unexplained death in the young. J Am Coll Cardiol. 2007;49: 240-246. (Pubitemid 46054388)
47. Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C, Vege A, Wang DW, Rhodes TE, George AL Jr, Schwartz PJ. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation. 2007;115:361-367. (Pubitemid 46148510)
48. Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K, Shkolnikova M, Berul CI, Bitner-Glindzicz M, Toivonen L, Horie M, Schulze-Bahr E, Denjoy I. The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation. 2006; 113:783-790.
49. Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005;294:2975-2980. (Pubitemid 41817658)
50. Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AAM, Ackerman MJ. Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009;6:1297-1303.
51. Ackerman MJ, Tester DJ, Porter CJ. Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc. 1999; 74:1088-1094. (Pubitemid 30243241)
52. Wilde AA, Jongbloed RJ, Doevendans PA, Duren DR, Hauer RN, Van Langen IM, Van Tintelen JP, Smeets HJ, Meyer H, Geelen JL. Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1). J Am Coll Cardiol. 1999;33:327-332. (Pubitemid 29234193)
53. Moss AJ, Robinson JL, Gessman L, Gillespie R, Zareba W, Schwartz PJ, Vincent GM, Benhorin J, Heilbron EL, Towbin JA, Priori SG, Napolitano C, Zhang L, Medina A, Andrews ML, Timothy K. Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with the long QT syndrome. Am J Cardiol. 1999;84:876-879. (Pubitemid 29475069)
54. Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, Denjoy I, Guicheney P, Breithardt G, Keating MT, Towbin JA, Beggs AH, Brink P, Wilde AA, Toivonen L, Zareba W, Robinson JL, Timothy KW, Corfield V, Wattanasirichaigoon D, Corbett C, Haverkamp W, Schulze-Bahr E, Lehmann MH, Schwartz K, Coumel P, Bloise R. Genotype- phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. 2001;103:89-95. (Pubitemid 32050441)
55. Khositseth A, Tester DJ, Will ML, Bell CM, Ackerman MJ. Identification of a common genetic substrate underlying postpartum cardiac events in congenital long QT syndrome. Heart Rhythm. 2004;1:60-64. (Pubitemid 38647252)
56. Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, Hofman N, Bikker H, Van Tintelen JP, Mannens MMAM, Wilde AAM, Ackerman MJ. The RYR2- encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: a comprehensive open reading frame mutational analysis. J Am Coll Cardiol. 2009;54:2065-2074.
57. Khositseth A, Ackerman MJ. Clinical evaluation, risk stratification, and management of congenital long QT syndrome. In: Gussak I, Antzelevitch C, eds. Contemporary Cardiology: Cardiac Repolarization: Bridging Basic and Clinical Science. Totowa, NJ: Humana Press; 2003:447-479.
58. Moss AJ, Windle JR, Hall WJ, Zareba W, Robinson JL, McNitt S, Severski P, Rosero S, Daubert JP, Qi M, Cieciorka M, Manalan AS. Safety and efficacy of flecainide in subjects with long QT-3 syndrome (DeltaKPQ mutation): a randomized, double-blind, placebo-controlled clinical trial. Ann Noninvasive Electrocardiol. 2005;10(suppl):59-66. (Pubitemid 44933555)
59. Moss AJ, Zareba W, Schwarz KQ, Rosero S, McNitt S, Robinson JL. Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J Cardiovasc Electrophysiol. 2008; 19:1289-1293.
60. Moss AJ, Zareba W, Kaufman ES, Gartman E, Peterson DR, Benhorin J, Towbin JA, Keating MT, Priori SG, Schwartz PJ, Vincent GM, Robinson JL, Andrews ML, Feng C, Hall WJ, Medina A, Zhang L, Wang Z. Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel. Circulation. 2002;105:794-799. (Pubitemid 34174917)
61. Jons C, Moss AJ, Lopes CM, McNitt S, Zareba W, Goldenberg I, Qi M, Wilde AAM, Shimizu W, Kanters JK, Towbin JA, Ackerman MJ, Robinson JL. Mutations in conserved amino acids in the KCNQ1 channel and risk of cardiac events in type-1 long-QT syndrome. J Cardiovasc Electrophysiol. 2009;20:859-865.
62. Shimizu W, Horie M, Ohno S, Takenaka K, Yamaguchi M, Shimizu M, Washizuka T, Aizawa Y, Nakamura K, Ohe T, Aiba T, Miyamoto Y, Yoshimasa Y, Towbin JA, Priori SG, Kamakura S. 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. 2004;44:117-125. (Pubitemid 38968469)
63. Moss AJ, Shimizu W, Wilde AAM, Towbin JA, Zareba W, Robinson JL, Qi M, Vincent GM, Ackerman MJ, Kaufman ES, Hofman N, Seth R, Kamakura S, Miyamoto Y, Goldenberg I, Andrews ML, McNitt S. Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007;115:2481-2489. (Pubitemid 46763221)
64. Nagaoka I, Shimizu W, Itoh H, Yamamoto S, Sakaguchi T, Oka Y, Tsuji K, Ashihara T, Ito M, Yoshida H, Ohno S, Makiyama T, Miyamoto Y, Noda T, Kamakura S, Akao M, Horie M. Mutation site dependent variability of cardiac events in Japanese LQT2 form of congenital long-QT syndrome. Circ J. 2008;72:694-699. (Pubitemid 351716671)
65. Shimizu W, Moss A, Wilde A, Towbin J, Ackerman M, Tester D, January C, Zareba W, Robinson J, Qi M, Vincent G, Kaufman E, Hofman N, Noda T, Kamakura S, Miyamoto Y, Shah S, Amin V, Goldenberg I, Andrews M, McNitt S. Genotype-phenotype aspects of type-2 long-QT syndrome. J Am Coll Cardiol. 2009;54:2052-2062.
66. Priori SG, Napolitano C, Memmi M, Colombi B, Drago F, Gasparini M, DeSimone L, Coltorti F, Bloise R, Keegan R, Cruz Filho FE, Vignati G, Benatar A, DeLogu A. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2002;106:69-74. (Pubitemid 34747444)
67. Tester DJ, Kopplin LJ, Will ML, Ackerman MJ. Spectrum and prevalence of cardiac ryanodine receptor (RyR2) mutations in a cohort of unrelated patients referred explicitly for long QT syndrome genetic testing. Heart Rhythm. 2005;2:1099-1105. (Pubitemid 41472159)
68. Eldar M, Pras E, Lahat H. A missense mutation in the CASQ2 gene is associated with autosomal-recessive catecholamine-induced polymorphic ventricular tachycardia. Trends Cardiovasc Med. 2003;13:148-151. (Pubitemid 36547683)
69. Tester DJ, Arya P, Will M, Haglund CM, Farley AL, Makielski JC, Ackerman MJ. Genotypic heterogeneity and phenotypic mimicry among unrelated patients referred for catecholaminergic polymorphic ventricular tachycardia genetic testing. Heart Rhythm. 2006;3:800-805. (Pubitemid 43960545)
70. Chen PS, Priori SG. The Brugada syndrome. J Am Coll Cardiol. 2008; 51:1176-1180.
71. Sarkozy A, Brugada P. Sudden cardiac death: what is inside our genes? Can J Cardiol. 2005;21:1099-1110. (Pubitemid 41723281)
72. Probst V, Denjoy I, Meregalli PG, Amirault JC, Sacher F, Mansourati J, Babuty D, Villain E, Victor J, Schott JJ, Lupoglazoff JM, Mabo P, Veltmann C, Jesel L, Chevalier P, Clur SA, Haissaguerre M, Wolpert C, Le Marec H, Wilde AA. Clinical aspects and prognosis of Brugada syndrome in children. Circulation. 2007;115:2042-2048. (Pubitemid 46625955)
73. Kapplinger J, Tester D, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann T, Miyamoto Y, Pfeiffer R, Pollevick G, Probst V, Zumhagen S, Vatta M, Towbin J, Shimizu W, Schulze-Bahr E, Antzelevitch C, Salisbury B, Guicheney P, Wilde A, Brugada R, Schott J, Ackerman M. An international compendium of mutations in the SCN5Aencoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2009;7:33-46.
74. Meregalli PG, Tan HL, Probst V, Koopmann TT, Tanck MW, Bhuiyan ZA, Sacher F, Kyndt F, Schott J-J, Albuisson J, Mabo P, Bezzina CR, Le Marec H, Wilde AAM. Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm. 2009;6:341-348.
75. London B, Michalec M, Mehdi H, Zhu X, Kerchner L, Sanyal S, Viswanathan PC, Pfahnl AE, Shang LL, Madhusudanan M, Baty CJ, Lagana S, Aleong R, Gutmann R, Ackerman MJ, McNamara DM, Weiss R, Dudley SC Jr. Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na- current and causes inherited arrhythmias. Circulation. 2007;116:2260-2268.
76. Watanabe H, Koopmann TT, Le SS, Yang T, Ingram CR, Schott JJ, Demolombe S, Probst V, Anselme F, Escande D, Wiesfeld AC, Pfeufer A, Kaab S, Wichmann HE, Hasdemir C, Aizawa Y, Wilde AA, Roden DM, Bezzina CR. Sodium channel-1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest. 2008;118:2260-2268.
77. Hu D, Barajas-Martinez H, Burashnikov E, Springer M, Wu Y, Varro A, Pfeiffer R, Koopmann TT, Cordeiro JM, Guerchicoff A, Pollevick GD, Antzelevitch C. A mutation in the beta3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype. Circ Cardiovasc Genet. 2009;2:270-278.
78. Antzelevitch C, Pollevick GD, Cordeiro JM, Casis O, Sanguinetti MC, Aizawa Y, Guerchicoff A, Pfeiffer R, Oliva A, Wollnik B, Gelber P, Bonaros EP Jr, Burashnikov E, Wu Y, Sargent JD, Schickel S, Oberheiden R, Bhatia A, Hsu LF, Haissaguerre M, Schimpf R, Borggrefe M, Wolpert C. Loss-offunction mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation. 2007;115:442-449. (Pubitemid 46184195)
79. Delpon E, Cordeiro JM, Nunez L, Bloch Thomsen PE, Guerchicoff A, Pollevick GD, Wu Y, Kanters JK, Larsen CT, Burashnikov E, Christiansen M, Antzelevitch C. Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome. Circ Arrhythm Electrophysiol. 2008;1:209-218.