American Journal of Cardiology
Volume 106, Issue 8 , Pages 1124-1128 , 15 October 2010

Prevalence and Spectrum of Large Deletions or Duplications in the Major Long QT Syndrome-Susceptibility Genes and Implications for Long QT Syndrome Genetic Testing

  • David J. Tester, BS

      Affiliations

    • Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics/Divisions of Cardiovascular Diseases and Pediatric Cardiology/Windland Smith Rice Sudden Death Genomics Laboratory, Rochester, Minnesota
    • ,
  • Amber J. Benton, BS

      Affiliations

    • Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics/Divisions of Cardiovascular Diseases and Pediatric Cardiology/Windland Smith Rice Sudden Death Genomics Laboratory, Rochester, Minnesota
    • ,
  • Laura Train, BS

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
    • ,
  • Barbara Deal, MD

      Affiliations

    • Division of Cardiology, Children's Memorial Hospital, Chicago, Illinois
    • ,
  • Linnea M. Baudhuin, PhD

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
    • ,
  • Michael J. Ackerman, MD, PhD

      Affiliations

    • Departments of Medicine, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics/Divisions of Cardiovascular Diseases and Pediatric Cardiology/Windland Smith Rice Sudden Death Genomics Laboratory, Rochester, Minnesota
    • Corresponding Author InformationCorresponding author: Tel: 507-284-0101; fax: 507-284-3757

Received 16 March 2010 ,Revised 2 June 2010 ,Accepted 2 June 2010.

References 

  1. Koopmann TT, Alders M, Jongbloed RJ, Guerrero S, Mannens M, Wilde AAM, et al. 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
  2. Eddy C-A, MacCormick JM, Chung S-K, Crawford JR, Love DR, Rees MI, et al. Identification of large gene deletions and duplications in KCNQ1 and KCNH2 in patients with long QT syndrome [see comment]. Heart Rhythm. 2008;5:1275–1281
  3. Caselli R, Mencarelli MA, Papa FT, Ariani F, Longo I, Meloni I, et al. Delineation of the phenotype associated with 7q36.1q36.2 deletion: long QT syndrome, renal hypoplasia and mental retardation. Am J Med Genet A. 2008;146:1195–1199
  4. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome (An update). Circulation. 1993;88:782–784
  5. Splawski I, Shen J, Timothy K, Vincent GM, Lehmann MH, Keating MT. Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. Genomics. 1998;51:86–97
  6. 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
  7. 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;80:805–811
  8. Mohler PJ, Schott J-J, 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;421:634–639
  9. 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;97:175–187
  10. Andelfinger G, Tapper AR, Welch RC, Vanoye CG, George AL, Benson DW. KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. Am J Hum Genet. 2002;71:663–668
  11. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, et al. Cav1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004;119:19–31
  12. Vatta M, Ackerman MJ, Ye B, Makielski JC, Ughanze EE, Taylor EW, et al. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation. 2006;114:2104–2112
  13. Medeiros-Domingo A, Kaku T, Tester DJ, Iturralde-Torres P, Itty A, Ye B, et al. SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome. Circulation. 2007;116:134–142
  14. Chen L, Marquardt ML, Tester DJ, Sampson KJ, Ackerman MJ, Kass RS. Mutation of an A-kinase-anchoring protein causes long-QT syndrome. Proc Natl Acad Sci U S A. 2007;104:20990–20995
  15. Ueda K, Valdivia CR, Medeiros-Domingo A, Tester DJ, Vatta M, Farrugia G, et al. Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc Natl Acad Sci U S A. 2008;105:9355–9360
  16. Koopmann TT, Beekman L, Alders M, Meregalli PG, Mannens MMAM, Moorman AFM, et al. Exclusion of multiple candidate genes and large genomic rearrangements in SCN5A in a Dutch Brugada syndrome cohort. Heart Rhythm. 2007;4:752–755
  17. Moss AJ, Shimizu W, Wilde AAM, Towbin JA, Zareba W, Robinson JL, et al. 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
  18. Tester DJ, Ackerman MJ. Sudden infant death syndrome: how significant are the cardiac channelopathies?. Cardiovasc Res. 2005;67:388–396
  19. Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C, et al. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation. 2007;115:361–367

 Dr. Ackerman received support from the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program, Rochester, Minnesota, and Grant HD42569 from the National Institutes of Health, Bethesda, Maryland.

PII: S0002-9149(10)01209-9

doi: 10.1016/j.amjcard.2010.06.022

American Journal of Cardiology
Volume 106, Issue 8 , Pages 1124-1128 , 15 October 2010

Article Tools

* Image Usage & Resolution