Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 3 May 1991:
Vol. 252. no. 5006, pp. 704 - 706
DOI: 10.1126/science.1673802

Articles

Science, Vol 252, Issue 5006, 704-706
Copyright © 1991 by American Association for the Advancement of Science


articles

Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene

M Keating, D Atkinson, C Dunn, K Timothy, GM Vincent, and M Leppert

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84132.

Genetic factors contribute to heart disease. In this study, linkage analyses have been performed in a family that is predisposed to sudden death from cardiac arrhythmias, the long QT syndrome (LQT). A DNA marker at the Harvey ras-1 locus (H-ras-1) was linked to LQT with a logarithm of the likelihood ratio for linkage (lod score) of 16.44 at theta = 0, which confirms the genetic basis of this trait and localizes this gene to the short arm of chromosome 11. As no recombination was observed between LQT and H-ras-1, and there is a physiological rationale for its involvement in this disease, ras becomes a candidate for the disease locus.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Genotyping Has a Minor Role in Selecting Therapy for Congenital Long-QT Syndromes at Present.
G. M. Vincent (2008)
Circ Arrhythmia Electrophysiol 1, 227-233
   Full Text »    PDF »
Electrophysiological Interventions for Inherited Arrhythmia Syndromes.
E. A. Stephenson and C. I. Berul (2007)
Circulation 116, 1062-1080
   Full Text »    PDF »
Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: do we need a scoring system?.
N. Hofman, A. A.M. Wilde, S. Kaab, I. M. van Langen, M. W.T. Tanck, M. M.A.M. Mannens, M. Hinterseer, B.-M. Beckmann, and H. L. Tan (2007)
Eur. Heart J. 28, 575-580
   Abstract »    Full Text »    PDF »
Clinical diagnosis of long QT syndrome: back to the caliper.
T. Rossenbacker and S. G. Priori (2007)
Eur. Heart J. 28, 527-528
   Full Text »    PDF »
The long QT syndrome: Therapeutic implications of a genetic diagnosis.
W. Shimizu (2005)
Cardiovasc Res 67, 347-356
   Abstract »    Full Text »    PDF »
Short QT syndrome.
R. Schimpf, C. Wolpert, F. Gaita, C. Giustetto, and M. Borggrefe (2005)
Cardiovasc Res 67, 357-366
   Abstract »    Full Text »    PDF »
Inaugural Article: Biography of Mark T. Keating.
R. Nuzzo (2005)
PNAS 102, 8086-8088
   Full Text »    PDF »
25th Anniversary of the International Long-QT Syndrome Registry: An Ongoing Quest to Uncover the Secrets of Long-QT Syndrome.
A. J. Moss and P. J. Schwartz (2005)
Circulation 111, 1199-1201
   Full Text »    PDF »
Modelling of short QT syndrome in a heterogeneous model of the human ventricular wall.
D. L. Weiss, G. Seemann, F. B. Sachse, and O. Dössel (2005)
Europace 7, S105-S117
   Abstract »    Full Text »    PDF »
Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: Multicenter study in Japan.
W. Shimizu, M. Horie, S. Ohno, K. Takenaka, M. Yamaguchi, M. Shimizu, T. Washizuka, Y. Aizawa, K. Nakamura, T. Ohe, et al. (2004)
J. Am. Coll. Cardiol. 44, 117-125
   Abstract »    Full Text »    PDF »
The year in electrophysiology.
D. P. Zipes (2004)
J. Am. Coll. Cardiol. 43, 1306-1314
   Full Text »    PDF »
Pharmacological Activation of Normal and Arrhythmia-Associated Mutant KCNQ1 Potassium Channels.
G. Seebohm, M. Pusch, J. Chen, and M. C. Sanguinetti (2003)
Circ. Res. 93, 941-947
   Abstract »    Full Text »    PDF »
A Candidate Locus Approach Identifies a Long QT Syndrome Gene Mutation.
T. A. Beery, M. Dyment, K. Shooner, T. K. Knilans, and D. W. Benson (2003)
Biol Res Nurs 5, 97-104
   Abstract »    PDF »
The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions.
I. I. Gottesman and T. D. Gould (2003)
Am J Psychiatry 160, 636-645
   Abstract »    Full Text »    PDF »
Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome.
W. Shimizu, T. Noda, H. Takaki, T. Kurita, N. Nagaya, K. Satomi, K. Suyama, N. Aihara, S. Kamakura, K. Sunagawa, et al. (2003)
J. Am. Coll. Cardiol. 41, 633-642
   Abstract »    Full Text »    PDF »
Novel Insights in the Congenital Long QT Syndrome.
X. H.T. Wehrens, M. A. Vos, P. A. Doevendans, and H. J.J. Wellens (2002)
Ann Intern Med 137, 981-992
   Abstract »    Full Text »    PDF »
Characterization of a novel missense mutation E637K in the pore-S6 loop of HERG in a patient with long QT syndrome.
K. Hayashi, M. Shimizu, H. Ino, M. Yamaguchi, H. Mabuchi, N. Hoshi, and H. Higashida (2002)
Cardiovasc Res 54, 67-76
   Abstract »    Full Text »    PDF »
Genotype and Severity of Long QT Syndrome.
J. A. Towbin, Z. Wang, and H. Li (2001)
Drug Metab. Dispos. 29, 574-579
   Abstract »    Full Text »
The long QT syndrome.
S. G. Priori, R. Bloise, and L. Crotti (2001)
Europace 3, 16-27
   PDF »
Spectrum of Mutations in Long-QT Syndrome Genes : KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.
I. Splawski, J. Shen, K. W. Timothy, M. H. Lehmann, S. Priori, J. L. Robinson, A. J. Moss, P. J. Schwartz, J. A. Towbin, G. M. Vincent, et al. (2000)
Circulation 102, 1178-1185
   Abstract »    Full Text »    PDF »
The long QT syndromes: genetic basis and clinical implications.
C.-E. Chiang and D. M. Roden (2000)
J. Am. Coll. Cardiol. 36, 1-12
   Abstract »    Full Text »    PDF »
Effects of Flecainide in Patients With New SCN5A Mutation : Mutation-Specific Therapy for Long-QT Syndrome?.
J. Benhorin, R. Taub, M. Goldmit, B. Kerem, R. S. Kass, I. Windman, and A. Medina (2000)
Circulation 101, 1698-1706
   Abstract »    Full Text »    PDF »
Long-Term Follow-Up of Patients With Long-QT Syndrome Treated With {beta}-Blockers and Continuous Pacing.
P. C. Dorostkar, M. Eldar, B. Belhassen, and M. M. Scheinman (1999)
Circulation 100, 2431-2436
   Abstract »    Full Text »    PDF »
Voltage-shift of the current activation in HERG S4 mutation (R534C) in LQT2.
T. Nakajima, T. Furukawa, Y. Hirano, T. Tanaka, H. Sakurada, T. Takahashi, R. Nagai, T. Itoh, Y. Katayama, Y. Nakamura, et al. (1999)
Cardiovasc Res 44, 283-293
   Abstract »    Full Text »    PDF »
Voltage-Gated Ion Channels and Hereditary Disease.
F. Lehmann-Horn and K. Jurkat-Rott (1999)
Physiol Rev 79, 1317-1372
   Abstract »    Full Text »    PDF »
C-terminal HERG Mutations : The Role of Hypokalemia and a KCNQ1-Associated Mutation in Cardiac Event Occurrence.
M. Berthet, I. Denjoy, C. Donger, L. Demay, H. Hammoude, D. Klug, E. Schulze-Bahr, P. Richard, H. Funke, K. Schwartz, et al. (1999)
Circulation 99, 1464-1470
   Abstract »    Full Text »    PDF »
Homozygous Deletion in KVLQT1 Associated With Jervell and Lange-Nielsen Syndrome.
Q. Chen, D. Zhang, R. L. Gingell, A. J. Moss, C. Napolitano, S. G. Priori, P. J. Schwartz, E. Kehoe, J. L. Robinson, E. Schulze-Bahr, et al. (1999)
Circulation 99, 1344-1347
   Abstract »    Full Text »    PDF »
Low Penetrance in the Long-QT Syndrome : Clinical Impact.
S. G. Priori, C. Napolitano, and P. J. Schwartz (1999)
Circulation 99, 529-533
   Abstract »    Full Text »    PDF »
Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1).
A. A. M. Wilde, R. J. E. Jongbloed, P. A. Doevendans, D. R. Duren, R. N. W. Hauer, I. M. van Langen, J. P. van Tintelen, H. J. M. Smeets, H. Meyer, and J. L. M. C. Geelen (1999)
J. Am. Coll. Cardiol. 33, 327-332
   Abstract »    Full Text »    PDF »
Impact of Laboratory Molecular Diagnosis on Contemporary Diagnostic Criteria for Genetically Transmitted Cardiovascular Diseases: Hypertrophic Cardiomyopathy, Long-QT Syndrome, and Marfan Syndrome : A Statement for Healthcare Professionals From the Councils on Clinical Cardiology, Cardiovascular Disease in the Young, and Basic Science, American Heart Association.
B. J. Maron, J. H. Moller, C. E. Seidman, G. M. Vincent, H. C. Dietz, A. J. Moss, J. A. Towbin, H. M. Sondheimer, R. E. Pyeritz, G. McGee, et al. (1998)
Circulation 98, 1460-1471
   Full Text »    PDF »
Novel Mechanism of HERG Current Suppression in LQT2 : Shift in Voltage Dependence of HERG Inactivation.
T. Nakajima, T. Furukawa, T. Tanaka, Y. Katayama, R. Nagai, Y. Nakamura, and M. Hiraoka (1998)
Circ. Res. 83, 415-422
   Abstract »    Full Text »    PDF »
Age- and Sex-Related Differences in Clinical Manifestations in Patients With Congenital Long-QT Syndrome : Findings From the International LQTS Registry.
E. H. Locati, W. Zareba, A. J. Moss, P. J. Schwartz, G. M. Vincent, M. H. Lehmann, J. A. Towbin, S. G. Priori, C. Napolitano, J. L. Robinson, et al. (1998)
Circulation 97, 2237-2244
   Abstract »    Full Text »    PDF »
New Mutations in the KVLQT1 Potassium Channel That Cause Long-QT Syndrome.
H. Li, Q. Chen, A. J. Moss, J. Robinson, V. Goytia, J. C. Perry, G. M. Vincent, S. G. Priori, M. H. Lehmann, S. W. Denfield, et al. (1998)
Circulation 97, 1264-1269
   Abstract »    Full Text »    PDF »
Relation between bradycardia dependent long QT syndrome and QT prolongation by disopyramide in humans.
H. Furushima, S. Niwano, M. Chinushi, K. Ohhira, A. Abe, and Y. Aizawa (1998)
Heart 79, 56-58
   Abstract »    Full Text »    PDF »
Prospects for adenovirus-mediated gene therapy of inherited diseases of the myocardium.
N. E. Bowles, Q. Wang, and J. A. Towbin (1997)
Cardiovasc Res 35, 422-430
   Full Text »    PDF »
Molecular Basis of the Long-QT Syndrome Associated with Deafness.
I. Splawski, K. W. Timothy, G. M. Vincent, D. L. Atkinson, and M. T. Keating (1997)
N. Engl. J. Med. 336, 1562-1567
   Full Text »    PDF »
Differential electrophysiology of repolarisation from clone to clinic.
R. Coronel, T. Opthof, P. Taggart, J. Tytgat, and M. Veldkamp (1997)
Cardiovasc Res 33, 503-517
   PDF »
Four Novel KVLQT1 and Four Novel HERG Mutations in Familial Long-QT Syndrome.
T. Tanaka, R. Nagai, H. Tomoike, S. Takata, K. Yano, K. Yabuta, N. Haneda, O. Nakano, A. Shibata, T. Sawayama, et al. (1997)
Circulation 95, 565-567
   Abstract »    Full Text »
Multiple Mechanisms in the Long-QT Syndrome: Current Knowledge, Gaps, and Future Directions.
D. M. Roden, R. Lazzara, M. Rosen, P. J. Schwartz, J. Towbin, and G. M. Vincent (1996)
Circulation 94, 1996-2012
   Abstract »    Full Text »
Genetically Defined Therapy of Inherited Long-QT Syndrome: Correction of Abnormal Repolarization by Potassium.
S. J. Compton, R. L. Lux, M. R. Ramsey, K. R. Strelich, M. C. Sanguinetti, L. S. Green, M. T. Keating, and J. W. Mason (1996)
Circulation 94, 1018-1022
   Abstract »    Full Text »
Lidocaine Block of LQT-3 Mutant Human Na+ Channels.
R.-H. An, R. Bangalore, S.Z. Rosero, and R.S. Kass (1996)
Circ. Res. 79, 103-108
   Abstract »    Full Text »
Construction of a YAC contig encompassing the Usher syndrome type 1C and familial hyperinsulinism loci on chromosome 11p14-15.1..
R Ayyagari, A Nestorowicz, Y Li, S Chandrasekharappa, C Chinault, P van Tuinen, R J Smith, J F Hejtmancik, and M A Permutt (1996)
Genome Res. 6, 504-514
   Abstract »    PDF »
Differential Response to Na+ Channel Blockade, ß-Adrenergic Stimulation, and Rapid Pacing in a Cellular Model Mimicking the SCN5A and HERG Defects Present in the Long-QT Syndrome.
S. G. Priori, C. Napolitano, F. Cantu, A. M. Brown, and P. J. Schwartz (1996)
Circ. Res. 78, 1009-1015
   Abstract »    Full Text »
Missense Mutation in the Pore Region of HERG Causes Familial Long QT Syndrome.
D. W. Benson, C. A. MacRae, M. R. Vesely, E. P. Walsh, J.G. Seidman, C. E. Seidman, and C. A. Satler (1996)
Circulation 93, 1791-1795
   Abstract »    Full Text »
Multiple Mechanisms of Na+ Channel– Linked Long-QT Syndrome.
R. Dumaine, Q. Wang, M. T. Keating, H. A. Hartmann, P. J. Schwartz, A. M. Brown, and G. E. Kirsch (1996)
Circ. Res. 78, 916-924
   Abstract »    Full Text »
Long QT Syndrome Patients With Gene Mutations.
M. R. Rosen (1995)
Circulation 92, 3373-3375
   Full Text »
Long QT Syndrome Patients With Mutations of the SCN5A and HERG Genes Have Differential Responses to Na+ Channel Blockade and to Increases in Heart Rate : Implications for Gene-Specific Therapy.
P. J. Schwartz, S. G. Priori, E. H. Locati, C. Napolitano, F. Cantu, J. A. Towbin, M. T. Keating, H. Hammoude, A. M. Brown, L.-S. K. Chen, et al. (1995)
Circulation 92, 3381-3386
   Abstract »    Full Text »
Congenital Long QT Syndromes : Toward Molecular Dissection of Arrhythmia Substrates.
A. A. Grace and K. R. Chien (1995)
Circulation 92, 2786-2789
   Full Text »
ECG T-Wave Patterns in Genetically Distinct Forms of the Hereditary Long QT Syndrome.
A. J. Moss, W. Zareba, J. Benhorin, E. H. Locati, W. J. Hall, J. L. Robinson, P. J. Schwartz, J. A. Towbin, G. M. Vincent, M. H. Lehmann, et al. (1995)
Circulation 92, 2929-2934
   Abstract »    Full Text »
New Revelations about the Long-QT Syndrome.
J. A. Towbin (1995)
N. Engl. J. Med. 333, 384-385
   Full Text »    PDF »
Genetic Approaches to Cardiovascular Disease : Supravalvular Aortic Stenosis, Williams Syndrome, and Long-QT syndrome.
M. T. Keating (1995)
Circulation 92, 142-147
   Abstract »    Full Text »
Gene for Progressive Familial Heart Block Type I Maps to Chromosome 19q13.
P. A. Brink, A. Ferreira, J. C. Moolman, H. W. Weymar, P.-L. van der Merwe, and V. A. Corfield (1995)
Circulation 91, 1633-1640
   Abstract »    Full Text »
Evidence of genetic heterogeneity in the long QT syndrome.
J Benhorin, Y. Kalman, A Medina, J Towbin, N Rave-Harel, T. Dyer, J Blangero, J. MacCluer, and B. Kerem (1993)
Science 260, 1960-1962
   PDF »
Response.
M. Keating (1993)
Science 260, 1962
   PDF »
Cardiac Ion Channels.
A. M. Katz (1993)
N. Engl. J. Med. 328, 1244-1251
   Full Text »
There Is More Than One Way to Collect Data for Linkage Analysis: What a Study of Epilepsy Can Tell Us About Linkage Strategy for Psychiatric Disease.
D. A. Greenberg (1992)
Arch Gen Psychiatry 49, 745-750
   Abstract »    PDF »
COULD A CANCER GENE CAUSE VENTRICULAR FIBRILLATION.
(1991)
Journal Watch (General) 1991, 7
   Full Text »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)