| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Articles |
1
Department of Clinical Biochemistry, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark.
2
Department of Medical Physiology, University of Copenhagen, DK-2200N Denmark.
3
Departments of Medicine B and
4
Pediatrics, Rigshospitalet, DK-2200Ø Copenhagen, Denmark.
5
Department of Pediatric Cardiology, Lund University Hospital, S-221 00 Lund, Sweden.
6
Department of Medical Genetics, Tromsø University Hospital, 9037 Tromsø, Norway.
7
Department of Cardiology, Regional Hospital of Trondheim, 7004 Trondheim, Norway.
aAddress correspondence to this author at: Department of Clinical Biochemistry, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Fax 45-32-68-38-78; e-mail mic{at}ssi.dk.
Background: The voltage-gated, rapid-delayed rectifier current (IKr) is important for repolarization of the heart, and mutations in the genes coding for the K+-ion channel conducting this current, i.e., KCNH2 for the 
-subunit HERG and KCNE2 for the ß-subunit MiRP1, cause acquired and congenital long Q-T syndrome (LQTS) and other cardiac arrhythmias.
Methods: We developed a robust single-strand conformation polymorphism-heteroduplex screening analysis, with identical thermocycling conditions for all PCR reactions, covering all of the coding exons in KCNH2 and KCNE2. The method was used to screen 40 unrelated LQTS patients.
Results: Eleven mutations, of which six were novel, were found in KCNH2. Interestingly, six mutations were found in the region of the gene coding for the Per-Arnt-Sim (PAS) and PAS-S1 regions of the HERG protein, stressing the need to examine the entire gene when screening for mutations. No mutations were found in KCNE2, suggesting that direct involvement of MiRP1 in LQTS is rare. Furthermore, four novel single-nucleotide polymorphisms (SNPs) and one amino acid polymorphism (R1047L) were identified in KCNH2, and one novel SNP and one previously known amino acid polymorphism (T8A) were found in KCNE2.
Conclusions: The potential role of rare polymorphisms in the HERG/MiRP1 K+-channel should be clarified with respect to drug interactions and susceptibility to arrhythmia and sudden death.
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  E. Delpon, J. M. Cordeiro, L. Nunez, P. E. B. Thomsen, A. Guerchicoff, G. D. Pollevick, Y. Wu, J. K. Kanters, C. T. Larsen, E. Burashnikov, et al. Functional Effects of KCNE3 Mutation and Its Role in the Development of Brugada Syndrome Circ Arrhythmia Electrophysiol, August 1, 2008; 1(3): 209 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Schulze-Bahr Arrhythmia Predisposition: Between Rare Disease Paradigms and Common Ion Channel Gene Variants J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A67 - A78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kaab and E. Schulze-Bahr Susceptibility genes and modifiers for cardiac arrhythmias Cardiovasc Res, August 15, 2005; 67(3): 397 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. C. Jones, E. C. Roti Roti, J. Wang, S. A. Delfosse, and G. A. Robertson Cardiac IKr Channels Minimally Comprise hERG 1a and 1b Subunits J. Biol. Chem., October 22, 2004; 279(43): 44690 - 44694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Anson, M. J. Ackerman, D. J. Tester, M. L. Will, B. P. Delisle, C. L. Anderson, and C. T. January Molecular and functional characterization of common polymorphisms in HERG (KCNH2) potassium channels Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2434 - H2441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. MacGregor The Future of Regulatory Toxicology: Impact of the Biotechnology Revolution Toxicol. Sci., October 1, 2003; 75(2): 236 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J Paavonen, H. Chapman, P. J Laitinen, H. Fodstad, K. Piippo, H. Swan, L. Toivonen, M. Viitasalo, K. Kontula, and M. Pasternack Functional characterization of the common amino acid 897 polymorphism of the cardiac potassium channel KCNH2 (HERG) Cardiovasc Res, September 1, 2003; 59(3): 603 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Mazzadi, X. Andre-Fouet, J. Duisit, V. Gebuhrer, N. Costes, P. Chevalier, C. Rodriguez, J.-J. Schott, H. Le Marec, P. Guicheney, et al. Cardiac retention of [11C]HED in genotyped long QT patients: a potential amplifier role for severity of the disease Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1286 - H1293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Murray, F Potet, C Bellocq, I Baro, W Reardon, H E Hughes, and S Jeffery Mutation in KCNQ1 that has both recessive and dominant characteristics J. Med. Genet., September 1, 2002; 39(9): 681 - 685. [Full Text] [PDF]
|
|
|
|
|
|
Q. Gong, C. L. Anderson, C. T. January, and Z. Zhou Role of glycosylation in cell surface expression and stability of HERG potassium channels Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H77 - H84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hayashi, M. Shimizu, H. Ino, M. Yamaguchi, H. Mabuchi, N. Hoshi, and H. Higashida Characterization of a novel missense mutation E637K in the pore-S6 loop of HERG in a patient with long QT syndrome Cardiovasc Res, April 1, 2002; 54(1): 67 - 76. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
