The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Sudden Death Associated With Short-QT Syndrome Linked to Mutations in HERG
Abstract
BACKGROUND: Sudden cardiac death takes the lives of more than 300 000 Americans annually. Malignant ventricular arrhythmias occurring in individuals with structurally normal hearts account for a subgroup of these sudden deaths. The present study describes the genetic basis for a new clinical entity characterized by sudden death and short-QT intervals in the ECG. METHODS AND RESULTS: Three families with hereditary short-QT syndrome and a high incidence of ventricular arrhythmias and sudden cardiac death were studied. In 2 of them, we identified 2 different missense mutations resulting in the same amino acid change (N588K) in the S5-P loop region of the cardiac IKr channel HERG (KCNH2). The mutations dramatically increase IKr, leading to heterogeneous abbreviation of action potential duration and refractoriness, and reduce the affinity of the channels to IKr blockers. CONCLUSIONS: We demonstrate a novel genetic and biophysical mechanism responsible for sudden death in infants, children, and young adults caused by mutations in KCNH2. The occurrence of sudden cardiac death in the first 12 months of life in 2 patients suggests the possibility of a link between KCNH2 gain of function mutations and sudden infant death syndrome. KCNH2 is the binding target for a wide spectrum of cardiac and noncardiac pharmacological compounds. Our findings may provide better understanding of drug interaction with KCNH2 and have implications for diagnosis and therapy of this and other arrhythmogenic diseases.
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In the citing paper
“Short QT syndrome KCNH2 KCNQ1 KCNJ2 CACNA1C CACNB2b IKr IKs IK1 ICa ICa Up to 70% 853, 856-858”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [856]
In the citing paper
“AF prevalence ranges from 5% to 20% in patients with long QT syndrome or Brugada syndrome, and is up to 70% in short QT syndrome (Table 20).853,[856][857][858]”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [856]
Citations
Cites
Zipes, D. P., & Wellens, H. J. J. (1998) · Circulation · doi:10.1161/01.cir.98.21.2334 · Cited by 2,744
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome
Curran, M. E., Splawski, I., Timothy, K. W., Vincent, G. M., Green, E. D., & Keating, M. T. (1995) · Cell · doi:10.1016/0092-8674(95)90358-5 · Cited by 2,253
Genetic basis and molecular mechanism for idiopathic ventricular fibrillation
Chen, Q., Kirsch, G. E., Zhang, D., Brugada, R., Brugada, J., Brugada, P., Potenza, D. R., Moya‐Mitjans, À., Borggrefe, M., BREITHARDT, G. E., et al. (1998) · Nature · doi:10.1038/32675 · Cited by 1,823
Sanguinetti, M. C., & Jurkiewicz, N. K. (1990) · The Journal of General Physiology · doi:10.1085/jgp.96.1.195 · Cited by 1,462
KCNQ1 Gain-of-Function Mutation in Familial Atrial Fibrillation
Chen, Y.-H., Xu, S.-J., Bendahhou, S., Wang, X.-L., Wang, Y., Xu, W.-Y., Jin, H., Sun, H., Su, X.-Y., Zhuang, Q.-N., et al. (2003) · Science · doi:10.1126/science.1077771 · Cited by 989
Short QT Syndrome: A Familial Cause of Sudden Death
Gaita, F., Giustetto, C., Bianchi, F., Wolpert, C., Schimpf, R., Riccardi, R., Grossi, S., Richiardi, E., & Borggrefe, M. (2003) · Circulation · doi:10.1161/01.cir.0000085071.28695.c4 · Cited by 708
Self-citationIdiopathic Short QT Interval:A New Clinical Syndrome?
Gussak, I. B., Brugada, P., Brugada, J., Wright, R. S., Kopecky, S. L., CHAITMAN, B. R., & Bjerregaard, P. (2000) · Cardiology · doi:10.1159/000047299 · Cited by 669
Multiple Mechanisms in the Long-QT Syndrome
Roden, D. M., Lazzara, R., Rosen, M. R., Schwartz, P. J., Towbin, J. A., & Vincent, G. M. (1996) · Circulation · doi:10.1161/01.cir.94.8.1996 · Cited by 631
Kyndt, F., Probst, V., Potet, F., Demolombe, S., Chevallier, J.-C., Baró, I., Moisan, J., Boisseau, P., Schott, J., Escande, D., et al. (2001) · Circulation · doi:10.1161/hc5001.100834 · Cited by 363
HERG, a Primary Human Ventricular Target of the Nonsedating Antihistamine Terfenadine
Roy, M. L., Dumaine, R., & Brown, A. M. (1996) · Circulation · doi:10.1161/01.cir.94.4.817 · Cited by 302
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P. F., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castellà, M., Diener, H., Heidbüchel, H., Hendriks, J., et al. (2016) · EP Europace · doi:10.1093/europace/euw295 · Cited by 6,438
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418
Calkins, H., Kuck, K. H., Cappato, R., Brugada, J., Camm, A. J., Chen, S.-A., Crijns, H. J. G., Damiano, R. J., Davies, D. W., DiMarco, J., et al. (2012) · Europace · doi:10.1093/europace/eus027 · Cited by 2,722
ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities
Epstein, A. E., DiMarco, J. P., Ellenbogen, K. A., Estes, N. A. M., Freedman, R. A., Gettes, L. S., Gillinov, A. M., Gregoratos, G., Hammill, S. C., Hayes, D. L., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.02.032 · Cited by 2,546
Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A. E., CHAITMAN, B. R., FROMER, M. A., Gregoratos, G., Klein, G. J., Myerburg, R. J., Quiñones, M. A., et al. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.07.010 · Cited by 1,975
Metadata
- Authors
- Brugada, R., Hong, K., Dumaine, R., Cordeiro, J., Gaita, F., Borggrefe, M., Menendez, T. M., Brugada, J., Pollevick, G. D., Wolpert, C., Burashnikov, E., Matsuo, K., Sheng Wu, Y., Guerchicoff, A., Bianchi, F., Giustetto, C., Schimpf, R., Brugada, P., & Antzelevitch, C.
- Affiliations
- From the Molecular Genetics (R.B., K.H., G.D.P., E.B., K.M., A.G.), Molecular Biology (R.D., Y.S.W.), and Experimental Cardiology (J.C., C.A.) Programs, Masonic Medical Research Laboratory, Utica, NY; Division of Cardiology (F.G., F.B., C.G.), Ospedale Mauriziano Umberto I, Torino, Italy; First Department of Medicine (M.B., C.W., R.S.), University Hospital Mannheim, University of Heidelberg, Mannheim, Germany; North Texas Heart Center (T.M.M.), Dallas, Tex; Arrhythmia Section (J.B.), Cardiovascular...
- Heidelberg University (DE)
- ORCID
- Venue
- Circulation
- Published
- 2004-01-06
- Volume
- 109
- Issue
- 1
- Pages
- 30-35
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2129393568
- Cited by
- 847
- References
- 27
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 22 · 2023: 16 · 2022: 14 · 2021: 25 · 2020: 31 · 2019: 22 · 2018: 29 · 2017: 48 · 2016: 29 · 2015: 28 · 2014: 35 · 2013: 48 · 2012: 58
- FWCI
- 31.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Keywords
- sudden cardiac death, short QT syndrome, hERG, KCNH2, gain-of-function mutations, ventricular arrhythmias, action potential duration, sudden infant death syndrome, drug interactions, hereditary arrhythmia
- MeSH terms
- ERG1 Potassium Channel, Adult, Arrhythmias, Cardiac, Cell Line, Electrocardiography, Female, Humans, Infant, Ion Channels, Male, Middle Aged, Syndrome, Death, Sudden, Cardiac, Genetic Heterogeneity, Mutation, Missense, Potassium Channels, Voltage-Gated, Ether-A-Go-Go Potassium Channels
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