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Genetic and Molecular Basis of Cardiac Arrhythmias Original Article

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

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Pages 53-63 | Published online: 08 Jul 2009

References

  • Schwartz PJ. Idiopathic long QT syndrome: progress and questions. Am Heart J 1985;109:399–411.
  • Ackerman MJ. The long QT syndrome: ion channel diseases of the heart. Mayo Clin Proc 1998;73:250–69.
  • Piippo K, Swan H, Pasternack M, Chapman H, Paavonen K, Viitasalo M, et al. A founder mutation of the potassium channel KCNQ1 in long QT syndrome: implications for estimation of disease prevalence and molecular diagnostics. J Am Coll Cardiol 2001;37:562–8.
  • Romano C. Congenital cardiac arrhythmia. Lancet 1965;l: 658–9.
  • Ward OC. A new familial cardiac syndrome in children. J Jr Med Assoc 1964;54:103–6.
  • Jervell A, Lange-Nielsen F. Congenital deaf-mutism, func-tional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J 1957;54:59–68.
  • Vincent GM, Timothy KW, Leppert M, Keating M. The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. N Engl J Med 1992;327:846–52.
  • Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswanathan PC, et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation 2002; 105: 1943–8.
  • Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 1996;12:17–23.
  • Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 1995;80:795–803.
  • Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT. Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat Genet 1997;17: 338–40.
  • Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, et al. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 1999;97:175–87.
  • Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995;80:805–11.
  • Mohler PJ, Schott JJ, Gramolini AO, Dilly KW, Guatimosim S, duBell WH, et al. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature 2003;421:634–9.
  • Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000;102: 1178–85.
  • Piippo K, Laitinen P, Swan H, Toivonen L, Viitasalo M, Pasternack M, et al. Homozygosity for a HERG potassium channel mutation causes a severe form of long QT syndrome: identification of an apparent founder mutation in the Finns. J Am Coll Cardiol 2000;35:1919–25.
  • Saarinen K, Swan H, Kainulainen K, Toivonen L, Viitasalo M, Kontula K. Molecular genetics of the long QT syndrome: two novel mutations of the KVLQT1 gene and phenotypic expression of the mutant gene in a large kindred. Hum Mutat 1998;11:158–65.
  • Laitinen P, Fodstad H, Piippo K, Swan H, Toivonen L, Viitasalo M, et al. Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects. Hum Mutat 2000;15:580–1.
  • Piippo K, Holmstrom S, Swan H, Viitasalo M, Raatikka M, Toivonen L, et al. Effect of the antimalarial drug halofantrine in the long QT syndrome due to a mutation of the cardiac sodium channel gene SCN5A. Am J Cardiol 2001;87:909–11.
  • Swan H, Viitasalo M, Piippo K, Laitinen P, Kontula K, Toivonen L. Sinus node function and ventricular repolariza-tion during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects. J Am Coll Cardiol 1999;34:823–9.
  • Kanters JK, Larsen LA, Orholm M, Agner E, Andersen PS, Vuust J, et al. Novel donor splice site mutation in the KVLQT1 gene is associated with long QT syndrome. J Cardiovasc Electrophysiol 1998;9:620–4.
  • Ackerman MJ, Tester DJ, Porter CJ. Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syn-drome. Mayo Clin Proc 1999;74:1088–94.
  • Liu W, Yang J, Hu D, Kang C, Li C, Zhang S, et al. KCNQ1 and KCNH2 mutations associated with long QT syndrome in a Chinese population. Hum Mutat 2002;20:475–6.
  • Wollnik B, Schroeder BC, Kubisch C, Esperer HD, Wieacker P, Jentsch T J. Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmias. Hum Mol Genet 19976:1943–9.
  • Splawski I, Shen J, Timothy KW, Vincent GM, Lehmann MH, Keating MT. Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. Genomics 1998;51:86–97.
  • Wei J, Fish FA, Myerburg RJ, Roden DM, George AL, Jr. Novel KCNQ1 mutations associated with recessive and dominant congenital long QT syndromes: evidence for variable hearing phenotype associated with R518X. Hum Mutat 2000;15:387–8.
  • Akimoto K, Furutani M, Imamura S, Furutani Y, Kasanuki H, Takao A, et al. Novel missense mutation (G6015) of HERG in a Japanese long QT syndrome family. Hum Mutat 1998;Suppl 1:S184–6.
  • Jongbloed RJ, Wilde AA, Geelen JL, Doevendans P, Schaap C, Van Langen I, et al. Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat 1999;13: 301–10.
  • Satler CA, Vesely MR, Duggal P, Ginsburg GS, Beggs AH. Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome. Hum Genet 1998; 102:265–72.
  • Wei J, Wang DW, Alings M, Fish F, Wathen M, Roden DM, et al. Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel. Circulation 1999;99:3165–71.
  • Iwasa H, Itoh T, Nagai R, Nakamura Y, Tanaka T. Twenty single nucleotide polymorphisms (SNPs) and their allelic frequencies in four genes that are responsible for familial long QT syndrome in the Japanese population. J Hum Genet 2000;45:182–3.
  • Smits JP, Eckardt L, Probst V, Bezzina CR, Schott JJ, Remme CA, et al. Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J Am Coll Cardiol 2002;40:350–6.
  • Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 2002;105:1342–7.
  • Tan HL, Bink-Boelkens MT, Bezzina CR, Viswanathan PC, Beaufort-Krol GC, van Tintelen PJ, et al. A sodium-channel mutation causes isolated cardiac conduction disease. Nature 2001;409:1043–7.
  • Bezzina CR, Rook MB, Groenewegen WA, Herfst LJ, van der Wal AC, Lam J, et al. Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system. Circ Res 2003;92:159–68.
  • 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;78:1479–87.
  • Larsen LA, Andersen PS, Kanters J, Svendsen IH, Jacobsen JR, Vuust J, et al. 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 2001;47:1390–5.
  • Lai LP, Deng CL, Moss AJ, Kass RS, Liang CS. Polymorphism of the gene encoding a human minimal potassium ion channel (minK). Gene 1994;151:339–40.
  • Tesson F, Donger C, Denjoy I, Berthet M, Bennaceur M, Petit C, et al. Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen syndrome. J Mol Cell Cardiol 1996; 28:2051–5.
  • Pietila E, Fodstad H, Niskasaari E, Laitinen PJ, Swan H, Savolainen M, et al. Association between HERG K897T polymorphism and QT interval in middle-aged Finnish women. J Am Coll Cardiol 2002;40:511–4.
  • Paavonen KJ, Chapman H, Laitinen PJ, Fodstad H, Piippo K, Swan H, et al. Functional characterization of the common amino acid 897 polymorphism of the cardiac potassium channel KCNH2 (HERG). Cardiovasc Res 2003;59:603–11.
  • Paulussen A, Matthijs G, Gewillig M, Verhasselt P, Cohen N, Aerssens J. Mutation analysis in congenital long QT syndrome-a case with missense mutations in KCNQ1 and SCN5A. Genet Test 2003;7:57–61.
  • Norio R, Nevanlinna HR, Perheentupa J. Hereditary diseases in Finland; rare flora in rare soil. Ann Clin Res 1973;5:109–41.
  • Norio R. Finnish Disease Heritage II: population prehistory and genetic roots of Finns. Hum Genet 2003;112:457–69.
  • Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M. Jervell and Lange-Nielsen syndrome: a Norwegian perspective. Am J Med Genet 1999;89:137–46.
  • Tyson J, Tranebjaerg L, Bellman S, Wren C, Taylor JF, Bathen J, et al. IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome. Hum Mol Genet 1997;6:2179–85.
  • Fraser GR, Froggatt P, Murphy T. Genetical aspects of the cardio-auditory syndrome of Jervell and Lange-Nielsen (con-genital deafness and electrocardiographic abnormalities). Ann Hum Genet 1964;28:133–57.
  • de Jager T, Corbett CH, Badenhorst JC, Brink PA, Corfield VA. Evidence of a long QT founder gene with varying phenotypic expression in South African families. J Med Genet 1996;33:567–73.
  • Larsen LA, Fosdal I, Andersen PS, Kanters JK, Vuust J, Wettrell G, et al. Recessive Romano-Ward syndrome asso-ciated with compound heterozygosity for two mutations in the KVLQT1 gene. Eur J Hum Genet 1999;7:724–8.
  • Tyson J, Tranebjaerg L, McEntagart M, Larsen LA, Chris-tiansen M, Whiteford ML, et al. Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen. Hum Genet 2000;107:499–503.
  • Van Langen IM, Birnie E, Alders M, Jongbloed RJ, Le Marec H, Wilde AA. The use of genotype-phenotype correlations in mutation analysis for the long QT syndrome. J Med Genet 2003;40:141–5.
  • Plaster NM, Tawil R, Tristani-Firouzi M, Canun S, Bend-ahhou S, Tsunoda A, et al. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Ander-sen's syndrome. Cell 2001;105: 511–9.
  • Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, et al. Functional and clinical characteriza-tion of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest 2002;110: 381–8.
  • Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long-QT syndrome: clinical impact. Circulation 1999;99:529–33.

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