|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2000; 36:1-12 © 2000 by the American College of Cardiology Foundation |
* Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Manuscript received October 28, 1999; revised manuscript received January 18, 2000, accepted March 27, 2000.
Reprint requests and correspondence: Chern-En Chiang, Division of Cardiology, Veterans General Hospital-Taipei, 201, Sec 2, Shih-Pai Road, Taipei, Taiwan
cechiang{at}vghtpe.gov.tw
It is becoming clear that mutations in the KVLQT1, human "ether-a-go-go" related gene, cardiac voltage-dependent sodium channel gene, minK and MiRP1 genes, respectively, are responsible for the LQT1, LQT2, LQT3, LQT5 and LQT6 variants of the Romano-Ward syndrome, characterized by autosomal dominant transmission and no deafness. The much rarer Jervell-Lange-Nielsen syndrome (with marked QT prolongation and sensorineural deafness) arises when a child inherits mutant KVLQT1 or minK alleles from both parents. In addition, some families are not linked to the known genetic loci. Cardiac voltage-dependent sodium channel gene encodes the cardiac sodium channel, and long QT syndrome (LQTS) mutations prolong action potentials by increasing inward plateau sodium current. The other mutations cause a decrease in net repolarizing current by reducing potassium currents through "dominant negative" or "loss of function" mechanisms. Polymorphic ventricular tachycardia (torsade de pointes) is thought to be initiated by early after- depolarizations in the Purkinje system and maintained by reentry in the myocardium. Clinical presentations vary with the specific gene affected and the specific mutation. Nevertheless, patients with identical mutations can also present differently, and some patients with LQTS mutations may have no manifest baseline phenotype. The question of whether the latter situation is one of high risk for administration of QT prolonging drugs or during myocardial ischemia is under active investigation. More generally, the identification of LQTS genes has provided tremendous new insights for our understanding of normal cardiac electrophysiology and its perturbation in a wide range of conditions associated with sudden death. It seems likely that the approach of applying information from the genetics of uncommon congenital syndromes to the study of common acquired diseases will be an increasingly important one in the next millennium.
| ||||||||||||||||||||||
This article has been cited by other articles:
|
|
 |
|
  C. Alonso-Ron, P. de la Pena, P. Miranda, P. Dominguez, and F. Barros Thermodynamic and Kinetic Properties of Amino-Terminal and S4-S5 Loop HERG Channel Mutants under Steady-State Conditions Biophys. J., May 15, 2008; 94(10): 3893 - 3911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. L. Bett and R. L. Rasmusson Modification of K+ channel-drug interactions by ancillary subunits J. Physiol., February 15, 2008; 586(4): 929 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. R. Boulet, A. J. Labro, A. L. Raes, and D. J. Snyders Role of the S6 C-terminus in KCNQ1 channel gating J. Physiol., December 1, 2007; 585(2): 325 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Giunti, G. Bruno, E. Lillaz, G. Gruden, V. Lolli, N. Chaturvedi, J. H. Fuller, M. Veglio, P. Cavallo-Perin, and The EURODIAB IDDM Complications Study Group Incidence and Risk Factors of Prolonged QTc Interval in Type 1 Diabetes: The EURODIAB Prospective Complications Study Diabetes Care, August 1, 2007; 30(8): 2057 - 2063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Heradien, A. Goosen, L. Crotti, G. Durrheim, V. Corfield, P. A. Brink, and P. J. Schwartz Does Pregnancy Increase Cardiac Risk for LQT1 Patients With the KCNQ1-A341V Mutation? J. Am. Coll. Cardiol., October 3, 2006; 48(7): 1410 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Vandenberg, A. Varghese, Y. Lu, J. A. Bursill, M. P. Mahaut-Smith, and C. L.-H. Huang Temperature dependence of human ether-a-go-go-related gene K+ currents Am J Physiol Cell Physiol, July 1, 2006; 291(1): C165 - C175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Sura Index of Suspicion in the Nursery NeoReviews, June 1, 2006; 7(6): e317 - e320. [Full Text] [PDF]
|
|
|
|
 |
|
 I. R. Boulet, A. L. Raes, N. Ottschytsch, and D. J. Snyders Functional effects of a KCNQ1 mutation associated with the long QT syndrome Cardiovasc Res, June 1, 2006; 70(3): 466 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M C S Hall and D M Todd Modern management of arrhythmias Postgrad. Med. J., February 1, 2006; 82(964): 117 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Kaufman Efficient Genotyping for Congenital Long QT Syndrome JAMA, December 21, 2005; 294(23): 3027 - 3028. [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Krahn, M. Gollob, R. Yee, L. J. Gula, A. C. Skanes, B. D. Walker, and G. J. Klein Diagnosis of Unexplained Cardiac Arrest: Role of Adrenaline and Procainamide Infusion Circulation, October 11, 2005; 112(15): 2228 - 2234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P.P. Smits, M. W. Veldkamp, C. R. Bezzina, Z. A. Bhuiyan, H. Wedekind, E. Schulze-Bahr, and A. A.M. Wilde Substitution of a conserved alanine in the domain IIIS4-S5 linker of the cardiac sodium channel causes long QT syndrome Cardiovasc Res, August 15, 2005; 67(3): 459 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Miranda, T. Giraldez, P. de la Pena, D. G Manso, C. Alonso-Ron, D. Gomez-Varela, P. Dominguez, and F. Barros Specificity of TRH receptor coupling to G-proteins for regulation of ERG K+ channels in GH3 rat anterior pituitary cells J. Physiol., August 1, 2005; 566(3): 717 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Chen, M. Inoue, and M. F. Sheets Reduced voltage dependence of inactivation in the SCN5A sodium channel mutation delF1617 Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2666 - H2676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zimetbaum and M. E. Josephson Is There a Role for Maintaining Sinus Rhythm in Patients with Atrial Fibrillation? Ann Intern Med, November 2, 2004; 141(9): 720 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Md. S. Amran, K. Hashimoto, and N. Homma Effects of Sodium-Calcium Exchange Inhibitors, KB-R7943 and SEA0400, on Aconitine-Induced Arrhythmias in Guinea Pigs in Vivo, in Vitro, and in Computer Simulation Studies J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 83 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Mohler, I. Splawski, C. Napolitano, G. Bottelli, L. Sharpe, K. Timothy, S. G. Priori, M. T. Keating, and V. Bennett A cardiac arrhythmia syndrome caused by loss of ankyrin-B function PNAS, June 15, 2004; 101(24): 9137 - 9142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Krumerman, X. Gao, J.-S. Bian, Y. F. Melman, A. Kagan, and T. V. McDonald An LQT mutant minK alters KvLQT1 trafficking Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1453 - C1463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Owczuk, M. A. Wujtewicz, W. Sawicka, M. Wujtewicz, and M. Swierblewski Is prolongation of the QTc interval during isoflurane anaesthesia more prominent in women pretreated with anthracyclines for breast cancer?{dagger} Br. J. Anaesth., May 1, 2004; 92(5): 658 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Etheridge, S. J. Compton, M. Tristani-Firouzi, and J. W. Mason A new oral therapy for long QT syndrome: Long-term oral potassium improves repolarization in patients with HERG mutations J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1777 - 1782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Torres, P. S. Bansal, M. Sunde, C. E. Clarke, J. A. Bursill, D. J. Smith, A. Bauskin, S. N. Breit, T. J. Campbell, P. F. Alewood, et al. Structure of the HERG K+ Channel S5P Extracellular Linker: ROLE OF AN AMPHIPATHIC {alpha}-HELIX IN C-TYPE INACTIVATION J. Biol. Chem., October 24, 2003; 278(43): 42136 - 42148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tosaka, M. C. Casimiro, Q. Rong, S. Tella, M. Oh, A. N. Katchman, J. C. Pezzullo, K. Pfeifer, and S. N. Ebert Nicotine Induces a Long QT Phenotype in Kcnq1-Deficient Mouse Hearts J. Pharmacol. Exp. Ther., September 1, 2003; 306(3): 980 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Savoye, D Klug, I Denjoy, P.V Ennezat, T Le Tourneau, P Guicheney, and S Kacet Tissue Doppler echocardiography in patients with long QT syndrome Eur J Echocardiogr, September 1, 2003; 4(3): 209 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-X. Yan, R. S. Lankipalli, J. F. Burke, S. Musco, and P. R. Kowey Ventricular repolarization components on the electrocardiogram: Cellular basis and clinical significance J. Am. Coll. Cardiol., August 6, 2003; 42(3): 401 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Al-Khatib, N. M. A. LaPointe, J. M. Kramer, and R. M. Califf What Clinicians Should Know About the QT Interval JAMA, April 23, 2003; 289(16): 2120 - 2127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.A. Groenewegen, C. R. Bezzina, J.P. van Tintelen, T. M. Hoorntje, M. M.A.M. Mannens, A. A.M. Wilde, Habo.J. Jongsma, and M. B. Rook A novel LQT3 mutation implicates the human cardiac sodium channel domain IVS6 in inactivation kinetics Cardiovasc Res, March 15, 2003; 57(4): 1072 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Goldschlager, A. E. Epstein, B. P. Grubb, B. Olshansky, E. Prystowsky, W. C. Roberts, M. M. Scheinman, and for the Practice Guidelines Subcommittee, North Am Etiologic Considerations in the Patient With Syncope and an Apparently Normal Heart Arch Intern Med, January 27, 2003; 163(2): 151 - 162. [Full Text] [PDF]
|
|
|
|
|
|
A. T. Yetman, R. A. Bornemeier, and B. W. McCrindle Long-term outcome in patients with Marfan syndrome: is aortic dissection the only cause of sudden death? J. Am. Coll. Cardiol., January 15, 2003; 41(2): 329 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hirano and M. Hiraoka Ca2+ Entry-Dependent Inactivation of L-Type Ca Current: A Novel Formulation for Cardiac Action Potential Models Biophys. J., January 1, 2003; 84(1): 696 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Chen and M. F. Sheets Enhancement of closed-state inactivation in long QT syndrome sodium channel mutation Delta KPQ Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H966 - H975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-E. Chiang, H.-N. Luk, T.-M. Wang, and P. Y.-A. Ding Prolongation of cardiac repolarization by arsenic trioxide Blood, August 28, 2002; 100(6): 2249 - 2252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Xu, J. J. Salata, J. Wang, Y. Wu, G.-X. Yan, T. Liu, R. A. Marinchak, and P. R. Kowey Increasing IKs corrects abnormal repolarization in rabbit models of acquired LQT2 and ventricular hypertrophy Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H664 - H670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-X. Yan, S. J. Rials, Y. Wu, T. Liu, X. Xu, R. A. Marinchak, and P. R. Kowey Ventricular hypertrophy amplifies transmural repolarization dispersion and induces early afterdepolarization Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1968 - H1975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wedekind, J. P.P. Smits, E. Schulze-Bahr, R. Arnold, M. W. Veldkamp, T. Bajanowski, M. Borggrefe, B. Brinkmann, I. Warnecke, H. Funke, et al. De Novo Mutation in the SCN5A Gene Associated With Early Onset of Sudden Infant Death Circulation, September 4, 2001; 104(10): 1158 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Brunner, W. Guo, G. F. Mitchell, P. D. Buckett, J. M. Nerbonne, and G. Koren Characterization of mice with a combined suppression of Ito and IK,slow Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1201 - H1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-X. Yan, Y. Wu, T. Liu, J. Wang, R. A. Marinchak, and P. R. Kowey Phase 2 Early Afterdepolarization as a Trigger of Polymorphic Ventricular Tachycardia in Acquired Long-QT Syndrome : Direct Evidence From Intracellular Recordings in the Intact Left Ventricular Wall Circulation, June 12, 2001; 103(23): 2851 - 2856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Laitinen, K. M. Brown, K. Piippo, H. Swan, J. M. Devaney, B. Brahmbhatt, E. A. Donarum, M. Marino, N. Tiso, M. Viitasalo, et al. Mutations of the Cardiac Ryanodine Receptor (RyR2) Gene in Familial Polymorphic Ventricular Tachycardia Circulation, January 30, 2001; 103(4): 485 - 490. [Abstract] [Full Text] [PDF]
|
|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
