Genetic testing for long-qt syndrome: Distinguishing pathogenic mutations from benign variants

Circulation

Volumn 120, Issue 18, 2009, Pages 1752-1760

  Kapa, Suraj ^a   Tester, David J ^b   Salisbury, Benjamin A ^d   Harris Kerr, Carole ^d   Pungliya, Manish S ^e   Alders, Marielle ^f   Wilde, Arthur A M ^g   Ackerman, Michael J ^a,b,c  

^a Division of Cardiovascular Diseases   (United States)

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

^c MAYO CLINIC   (United States)

^d PGxHealth LLC   (United States)

^e Clinical Data Inc   (United States)

^f Department of Clinical Genetics ^*

^g ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

Genetic testing; Genetics; Ion channels; Long QT syndrome; Mutations

Indexed keywords

POTASSIUM CHANNEL KCNQ1; SODIUM CHANNEL;

AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CONTROLLED STUDY; GENE; GENE LOCATION; GENE MUTATION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; KCNH2 GENE; LONG QT SYNDROME; MISSENSE MUTATION; PATHOGENESIS; PRIORITY JOURNAL; SCN5A GENE;

CASE-CONTROL STUDIES; ETHER-A-GO-GO POTASSIUM CHANNELS; ETHNIC GROUPS; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; GENETIC VARIATION; HUMANS; KCNQ1 POTASSIUM CHANNEL; LONG QT SYNDROME; MUSCLE PROTEINS; MUTATION; SODIUM CHANNELS;

EID: 70449359365     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.109.863076     Document Type: Article

References (29)

1. GeneTests. Medical Genetics Informational Resource (database online). Seattle, Wash: University of Washington; 1995-2007. Available at: http://www.ncbi.nlm.nih.gov/sites/GeneTests/?db = GeneTests. Accessed October 1, 2009.
2. Evans JP, Skrzynia C, Burke W. The complexities of predictive genetic testing. BMJ. 2001;322:1052-1056.
3. Hunter DJ, Khoury MJ, Drazen JM. Letting the genome out of the bottle: will we get our wish? N Engl J Med. 2008;358:105-107.
4. Shimizu W. The long QT syndrome: therapeutic implications of a genetic diagnosis. Cardiovasc Res. 2005;67:347-356.
5. Keating M, Atkinson D, Dunn C, Timothy K, Vincent GM, Leppert M. Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene. Science. 1991;252:704-706.
6. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995;80:805-811.
7. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmias: HERG mutations cause long QT syndrome. Cell. 1995;80:795-804.
8. Zareba W, Moss AJ, Schwartz PJ, Vincent GM, Robinson JL, Prior SG, Benhorin J, Locati EH, Towbin JA, Keating MT, Lehmann MH, Hall WJ, Andrews ML, Napolitano C, Timothy K, Zhang L, Medina A, MacCluer JW. Influence of the genotype on the clinical course of the long QT syndrome. N Engl J Med. 1998;339:960-965.
9. Schwartz PJ, Prior SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, Denjoy I, Guicheney P, Breithardt G, Keating MT, Towbin JA, Beggs AH, Brink P, Wilde AAM, 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. Geno-type-phenotype correlation in the long QT syndrome: gene specific triggers for life threatening arrhythmias. Circulation. 2001;103:89-95.
10. Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vincentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, Cappelletti D. Risk stratification in the long-QT syndrome. N Engl J Med. 2003;348: 1866-1874.
11. Zareba W. Genotype-specific ECG patterns in long QT syndrome. J Electrocardiol. 2006;39:S101-S106.
12. Napolitano C, Bloise R, Priori SG. Gene-specific therapy for inherited arrhythmogenic disorders. Pharmacol Ther. 2006;110:1-13.
13. Tan HL, Bardai A, Shimizu W, Moss AJ, Schulze-Bahr E, Noda T, Wilde AAM. Genotype-specific onset of arrhythmias in congenital long QT syndrome: possible therapy implications. Circulation. 2006;114: 2096-2103.
14. Moss AJ, Shimizu W, Wilde AAM, Towbin JA, Zareba W, Robinson JL, Qi M, Vincent M, Ackerman MJ, Kaufman ES, QHofman 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 bio-physical function of mutations involving the KCNQ1 gene. Circulation. 2007;115:2481-2489.
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. Ackerman MJ, Tester DJ, Jones GS, Will ML, Burrow CR, Curran ME. Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. Mayo Clin Proc. 2003;78:1479-1487.
17. Ackerman MJ, Splawski I, Makielski J, Tester D, Will M, Timothy K, Keating M, Jones G, Chadha M, Burrow C. Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Bru-gadalong QT syndrome genetic testing. Heart Rhythm. 2004;1:600-607.
18. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome: an update. Circulation. 1993;88:782-784.
19. 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. 2007;128:181-207.
20. Antonarakis SE. Recommendations for a nomenclature system for human gene mutations: Nomenclature Working Group. Hum Mutat. 1998; 11:1-3.
21. Splawski I, Shen J, Timothy KW, Vincent M, Lehmann MH, Keating MT. Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. Genomics. 1998;51:86-97.
22. Wang Q, Li Z, Shen J, Keating MT. Genomic organization of the human SCN5A gene encoding the cardiac sodium channel. Genomics. 1996; 34:9-16.
23. Neyroud N, Richard P, Vignier N, Donger C, Denjoy I, Demay L, Shkolnikova M, Pesce R, Chevalier P, Hanique B, Coumel P, Schwartz K, Guicheney P. Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome. Circ Res. 1999;84:290-297.
24. Grundy S, Cleeman J, Bairey Merz C, Brewer Jr H, Clark L, Hun-ninghake D, Pasternak R, Smith S Jr, Stone N. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. J Am Coll Cardiol. 2004;44:720-732.
25. Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE. A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet. 2007;81:873-883.
26. Tester DJ, Will ML, Haglund C, Ackerman MJ. Effect of clinical phe-notype on yield of long QT-syndrome genetic testing. J Am Coll Cardiol. 2006;47:764-768.
27. Worth CL, Bickerton GR, Schreyer A, Forman JR, Cheng TM, Lee S, Gong S, Burke DF, Blundell TL. A structural bioinformatics approach to the analysis of nonsynonymous single nucleotide polymorphisms (nsSNPs) and their relation to disease. J Bioinform Comput Biol. 2007; 5:1297-1318.
28. Lehnart SE, Ackerman MJ, Benson DW Jr, Brugada R, Clancy CE, Donahue JK, George AL Jr, Grant AO, Groft SC, January CT, Lathrop DA, Lederer WJ, Makielski JC, Mohler PJ, Moss A, Nerbonne JM, Olson TM, Przywara DA, Towbin JA, Wang LH, Marks AR. Inherited arrhythmias: a National Heart, Lung, and Blood Institute and Office of Rare Diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardio-myopathies of gene mutations affecting ion channel function. Circulation. 2007;116:2325-2345.
29. Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ, Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/ American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e385-e484.