Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing

BMC Cardiovascular Disorders

Volumn 12, Issue , 2012, Pages

  Stattin, Eva Lena ^a   Boström, Ida M ^a   Winbo, Annika ^a   Cederquist, Kristina ^a   Jonasson, Jenni ^a   Jonsson, Björn Anders ^a   Diamant, Ulla Britt ^a   Jensen, Steen M ^a   Rydberg, Annika ^a   Norberg, Anna ^a  

^a UMEÅ UNIVERSITY   (Sweden)

Author keywords

Arrhythmia; Founder mutation; Ion channel; Long QT syndrome; Variant of unknown significance

Indexed keywords

ADOLESCENT; ADULT; AGED; ARTICLE; CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA; CHILD; COHORT ANALYSIS; EXON; FAINTNESS; FEMALE; GENE; GENE DELETION; GENE DOSAGE; GENE DUPLICATION; GENE MUTATION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC RISK; GENETIC SCREENING; GENOTYPE; HETEROZYGOTE; HUMAN; HUMAN CELL; INFANT; KCNE1 GENE; KCNE2 GENE; KCNH2 GENE; KCNQ1 GENE; LONG QT SYNDROME; MAJOR CLINICAL STUDY; MALE; NUCLEOTIDE SEQUENCE; PRESCHOOL CHILD; PRIORITY JOURNAL; RELATIVE; RYR2 GENE; SCHOOL CHILD; SCN5A GENE; SUDDEN DEATH; SWEDEN;

ADOLESCENT; ADULT; AGED; CHILD; CHILD, PRESCHOOL; ELECTROCARDIOGRAPHY; FEMALE; GENETIC TESTING; GENOTYPE; HUMANS; INFANT; INFANT, NEWBORN; LONG QT SYNDROME; MALE; MIDDLE AGED; MUTATION;

EID: 84867742520     PISSN: None     EISSN: 14712261     Source Type: Journal    
DOI: 10.1186/1471-2261-12-95     Document Type: Article

References (45)

1. Goldenberg I, Zareba W, Moss AJ. Long QT Syndrome. Curr Probl Cardiol 2008, 33(11):629-694. 10.1016/j.cpcardiol.2008.07.002, 18835466.
2. Kramer DB, Zimetbaum PJ. Long-QT syndrome. Cardiol Rev 2011, 19(5):217-225. 10.1097/CRD.0b013e3182203504, 21808164.
3. Ackerman MJ. The long QT syndrome: ion channel diseases of the heart. Mayo Clin Proc 1998, 73(3):250-269. 10.4065/73.3.250, 9511785.
4. Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, et al. Risk stratification in the long-QT syndrome. N Engl J Med 2003, 348(19):1866-1874. 10.1056/NEJMoa022147, 12736279.
5. Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, Denjoy I, Guicheney P, Breithardt G, Keating MT, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001, 103(1):89-95. 10.1161/01.CIR.103.1.89, 11136691.
6. 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(2):327-332. 10.1016/S0735-1097(98)00578-6, 9973011.
7. Priori SG, Napolitano C, Memmi M, Colombi B, Drago F, Gasparini M, DeSimone L, Coltorti F, Bloise R, Keegan R, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002, 106(1):69-74. 10.1161/01.CIR.0000020013.73106.D8, 12093772.
8. Berge KE, Haugaa KH, Fruh A, Anfinsen OG, Gjesdal K, Siem G, Oyen N, Greve G, Carlsson A, Rognum TO, et al. Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers. Scand J Clin Lab Invest 2008, 68(5):362-368. 10.1080/00365510701765643, 18752142.
9. 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. Hear Rhythm 2005, 2(10):1099-1105.
10. Roden DM. Clinical practice. Long-QT syndrome. N Engl J Med 2008, 358(2):169-176. 10.1056/NEJMcp0706513, 18184962.
11. Bokil NJ, Baisden JM, Radford DJ, Summers KM. Molecular genetics of long QT syndrome. Mol Genet Metab 2010, 101(1):1-8. 10.1016/j.ymgme.2010.05.011, 20594883.
12. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000, 102(10):1178-1185. 10.1161/01.CIR.102.10.1178, 10973849.
13. 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. Hear Rhythm 2005, 2(5):507-517.
14. Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, et al. An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Hear Rhythm 2010, 7(1):33-46.
15. 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(23):2975-2980. 10.1001/jama.294.23.2975, 16414944.
16. Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M. Jervell and Lange-Nielsen syndrome: a Norwegian perspective. Am J Med Genet 1999, 89(3):137-146. 10.1002/(SICI)1096-8628(19990924)89:3<137::AID-AJMG4>3.0.CO;2-C, 10704188.
17. Fodstad H, Swan H, Laitinen P, Piippo K, Paavonen K, Viitasalo M, Toivonen L, Kontula K. Four potassium channel mutations account for 73% of the genetic spectrum underlying long-QT syndrome (LQTS) and provide evidence for a strong founder effect in Finland. Ann Med 2004, 36(Suppl 1):53-63.
18. Crotti L, Spazzolini C, Schwartz PJ, Shimizu W, Denjoy I, Schulze-Bahr E, Zaklyazminskaya EV, Swan H, Ackerman MJ, Moss AJ, et al. The common long-QT syndrome mutation KCNQ1/A341V causes unusually severe clinical manifestations in patients with different ethnic backgrounds: toward a mutation-specific risk stratification. Circulation 2007, 116(21):2366-2375. 10.1161/CIRCULATIONAHA.107.726950, 17984373.
19. Itoh H, Shimizu W, Hayashi K, Yamagata K, Sakaguchi T, Ohno S, Makiyama T, Akao M, Ai T, Noda T, et al. Long QT syndrome with compound mutations is associated with a more severe phenotype: a Japanese multicenter study. Hear Rhythm 2010, 7(10):1411-1418.
20. Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, Wilde AA, Ackerman MJ. Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation 2009, 120(18):1752-1760. 10.1161/CIRCULATIONAHA.109.863076, 3025752, 19841300.
21. Antonarakis SE. Recommendations for a nomenclature system for human gene mutations. Nomenclature Working Group. Hum Mutat 1998, 11(1):1-3.
22. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009, 4(7):1073-1081.
23. Sunyaev S, Ramensky V, Koch I, Lathe W, Kondrashov AS, Bork P. Prediction of deleterious human alleles. Hum Mol Genet 2001, 10(6):591-597. 10.1093/hmg/10.6.591, 11230178.
24. Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, Olivier M. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 2007, 28(6):622-629. 10.1002/humu.20495, 17311302.
25. Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ, Rhodes TH, George AL. Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest 2003, 112(7):1019-1028. 198523, 14523039.
26. Winbo A, Diamant UB, Rydberg A, Persson J, Jensen SM, Stattin EL. Origin of the Swedish long QT syndrome Y111C/KCNQ1 founder mutation. Hear Rhythm 2011, 8(4):541-547.
27. Jespersen T, Rasmussen HB, Grunnet M, Jensen HS, Angelo K, Dupuis DS, Vogel LK, Jorgensen NK, Klaerke DA, Olesen SP. Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif. J Cell Sci 2004, 117(Pt 19):4517-4526.
28. Dahimene S, Alcolea S, Naud P, Jourdon P, Escande D, Brasseur R, Thomas A, Baro I, Merot J. The N-terminal juxtamembranous domain of KCNQ1 is critical for channel surface expression: implications in the Romano-Ward LQT1 syndrome. Circ Res 2006, 99(10):1076-1083. 10.1161/01.RES.0000250262.12219.95, 17053194.
29. Winbo A, Diamant UB, Stattin EL, Jensen SM, Rydberg A. Low incidence of sudden cardiac death in a Swedish Y111C type 1 long-QT syndrome population. Circ Cardiovasc Genet 2009, 2(6):558-564. 10.1161/CIRCGENETICS.108.825547, 20031635.
30. Amin AS, Giudicessi JR, Tijsen AJ, Spanjaart AM, Reckman YJ, Klemens CA, Tanck MW, Kapplinger JD, Hofman N, Sinner MF, et al. Variants in the 3' untranslated region of the KCNQ1-encoded Kv7.1 potassium channel modify disease severity in patients with type 1 long QT syndrome in an allele-specific manner. Eur Heart J 2012, 33(6):714-723. 10.1093/eurheartj/ehr473, 3303714, 22199116.
31. Olsson M, Norgren N, Obayashi K, Plante-Bordeneuve V, Suhr OB, Cederquist K, Jonasson J. A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers. BMC Med Genet 2010, 11:130. 10.1186/1471-2350-11-130, 2945965, 20840742.
32. Wei J, Fish FA, Myerburg RJ, Roden DM, George AL. Novel KCNQ1 mutations associated with recessive and dominant congenital long QT syndromes: evidence for variable hearing phenotype associated with R518X. Hum Mutat 2000, 15(4):387-388.
33. Larsen LA, Fosdal I, Andersen PS, Kanters JK, Vuust J, Wettrell G, Christiansen M. Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene. Eur J Hum Genet 1999, 7(6):724-728. 10.1038/sj.ejhg.5200323, 10482963.
34. Winbo A, Stattin EL, Diamant UB, Persson J, Jensen SM, Rydberg A. Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden. Europace 2012, [Epub ahed of print].
35. Marjamaa A, Salomaa V, Newton-Cheh C, Porthan K, Reunanen A, Karanko H, Jula A, Lahermo P, Vaananen H, Toivonen L, et al. High prevalence of four long QT syndrome founder mutations in the Finnish population. Ann Med 2009, 41(3):234-240. 10.1080/07853890802668530, 2704397, 19160088.
36. Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, Hofman N, Bikker H, van Tintelen JP, Mannens MM, Wilde AA, 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(22):2065-2074. 10.1016/j.jacc.2009.08.022, 2880864, 19926015.
37. Koopmann TT, Alders M, Jongbloed RJ, Guerrero S, Mannens MM, Wilde AA, 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. Hear Rhythm 2006, 3(1):52-55.
38. Eddy CA, MacCormick JM, Chung SK, 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. Hear Rhythm 2008, 5(9):1275-1281.
39. Barc J, Briec F, Schmitt S, Kyndt F, Le Cunff M, Baron E, Vieyres C, Sacher F, Redon R, Le Caignec C, et al. Screening for copy number variation in genes associated with the long QT syndrome: clinical relevance. J Am Coll Cardiol 2011, 57(1):40-47. 10.1016/j.jacc.2010.08.621, 21185499.
40. Tester DJ, Benton AJ, Train L, Deal B, Baudhuin LM, Ackerman MJ. Prevalence and spectrum of large deletions or duplications in the major long QT syndrome-susceptibility genes and implications for long QT syndrome genetic testing. Am J Cardiol 2010, 106(8):1124-1128. 10.1016/j.amjcard.2010.06.022, 2950837, 20920651.
41. Imboden M, Swan H, Denjoy I, Van Langen IM, Latinen-Forsblom PJ, Napolitano C, Fressart V, Breithardt G, Berthet M, Priori S, et al. Female predominance and transmission distortion in the long-QT syndrome. N Engl J Med 2006, 355(26):2744-2751. 10.1056/NEJMoa042786, 17192539.
42. Westenskow P, Splawski I, Timothy KW, Keating MT, Sanguinetti MC. Compound mutations: a common cause of severe long-QT syndrome. Circulation 2004, 109(15):1834-1841. 10.1161/01.CIR.0000125524.34234.13, 15051636.
43. Refsgaard L, Holst AG, Sadjadieh G, Haunso S, Nielsen JB, Olesen MS. High prevalence of genetic variants previously associated with LQT syndrome in new exome data. Eur J Hum Genet 2012, 20:905-908. 10.1038/ejhg.2012.23, 3400735, 22378279.
44. Tester DJ, Valdivia C, Harris-Kerr C, Alders M, Salisbury BA, Wilde AA, Makielski JC, Ackerman MJ. Epidemiologic, molecular, and functional evidence suggest A572D-SCN5A should not be considered an independent LQT3-susceptibility mutation. Hear Rhythm 2010, 7(7):912-919.
45. Van Norstrand DW, Tester DJ, Ackerman MJ. Overrepresentation of the proarrhythmic, sudden death predisposing sodium channel polymorphism S1103Y in a population-based cohort of African-American sudden infant death syndrome. Hear Rhythm 2008, 5(5):712-715.