Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients
| Autor: | Aimee D C Paulussen, Giinter Breithardt, Martin Armstrong, Peter Verhasselt, Wilhelm Haverkamp, Jeroen Aerssens, Hubert J.M. Smeets, Pieter A. Doevendans, Ronaldus A. H. J. Gilissen, Nadine Cohen, Eric Schulze-Bahr |
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| Přispěvatelé: | Populatie Genetica, Cardiologie, Klinische Genetica, RS: CARIM School for Cardiovascular Diseases, RS: NUTRIM School of Nutrition and Translational Research in Metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male ERG1 Potassium Channel congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Potassium Channels Adolescent Long QT syndrome DNA Mutational Analysis Mutation Missense medicine.disease_cause QT interval Sodium Channels NAV1.5 Voltage-Gated Sodium Channel Sudden cardiac death Risk Factors Internal medicine Drug Discovery medicine Genetic predisposition Humans Missense mutation Genetics (clinical) Aged Aged 80 and over Mutation KCNQ Potassium Channels Models Genetic biology business.industry Genetic Variation KCNE2 Forme fruste Middle Aged medicine.disease Ether-A-Go-Go Potassium Channels Long QT Syndrome Endocrinology Potassium Channels Voltage-Gated KCNQ1 Potassium Channel Immunology biology.protein Molecular Medicine Female business |
| Zdroj: | Journal of Molecular Medicine, 82(3), 182-188. Springer |
| ISSN: | 1432-1440 0946-2716 |
| DOI: | 10.1007/s00109-003-0522-z |
| Popis: | Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients.Paulussen AD, Gilissen RA, Armstrong M, Doevendans PA, Verhasselt P, Smeets HJ, Schulze-Bahr E, Haverkamp W, Breithardt G, Cohen N, Aerssens J.Department of Pharmacogenomics, Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, Beerse, Belgium.Administration of specific drugs may occasionally induce acquired long QT syndrome (aLQTS), a disorder that predisposes to ventricular arrhythmias, typically of the torsade de pointes (TdP) type, and sudden cardiac death. "Forme fruste" mutations in congenital LQTS (cLQTS) genes have been reported repeatedly as the underlying cause of aLQTS, and are therefore considered as an important risk factor. We evaluated the impact of genetic susceptibility for aLQTS through mutations in cLQTS genes. Five cLQTS genes ( KCNH2, KCNQ1, SCN5A, KCNE1, KCNE2) were thoroughly screened for genetic variations in 32 drug-induced aLQTS patients with confirmed TdP and 32 healthy individuals. Missense forme frust mutations were identified in four aLQTS patients: D85N in KCNE1 (two cases), T8A in KCNE2, and P347S in KCNH2. Three other missense variations were found both in patients and controls, and are thus unlikely to significantly influence aLQTS susceptibility. In addition, 13 silent and six intronic variations were detected, four of which were found in a single aLQTS patient but not in the controls. We conclude that missense mutations in the examined cLQTS genes explain only a minority of aLQTS cases |
| Databáze: | OpenAIRE |
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