| Online-Ressource |
Verfasst von: | Cordeiro, Jonathan M. [VerfasserIn]  |
| Perez, Guillermo J. [VerfasserIn]  |
| Schmitt, Nicole [VerfasserIn]  |
| Pfeiffer, Ryan [VerfasserIn]  |
| Nesterenko, Vladislav V. [VerfasserIn]  |
| Burashnikov, Elena [VerfasserIn]  |
| Veltmann, Christian [VerfasserIn]  |
| Borggrefe, Martin [VerfasserIn]  |
| Wolpert, Christian [VerfasserIn]  |
| Schimpf, Rainer [VerfasserIn]  |
| Antzelevitch, Charles [VerfasserIn]  |
Titel: | Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2 |
Verf.angabe: | Jonathan M. Cordeiro, Guillermo J. Perez, Nicole Schmitt, Ryan Pfeiffer, Vladislav V. Nesterenko, Elena Burashnikov, Christian Veltmann, Martin Borggrefe, Christian Wolpert, Rainer Schimpf, Charles Antzelevitch |
E-Jahr: | 2010 |
Jahr: | 1 December 2010 |
Umfang: | 10 S. |
Fussnoten: | Gesehen am 16.06.2023 |
Titel Quelle: | Enthalten in: Canadian journal of physiology and pharmacology |
Ort Quelle: | Ottawa, Ont. : NRC Research Press, 1964 |
Jahr Quelle: | 2010 |
Band/Heft Quelle: | 88(2010), 12, Seite 1181-1190 |
ISSN Quelle: | 1205-7541 |
Abstract: | Long QT syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and potentially life-threatening arrhythmias. Mutations in 12 different genes have been associated with LQTS. Here we describe a patient with LQTS who has a mutation in KCNQ1 as well as a polymorphism in KCNH2. The proband (MMRL0362), a 32-year-old female, exhibited multiple ventricular extrasystoles and one syncope. Her ECG (QT interval corrected for heart rate (QTc) = 518ms) showed an LQT2 morphology in leads V4-V6 and LQT1 morphology in leads V1-V2. Genomic DNA was isolated from lymphocytes. All exons and intron borders of 7 LQTS susceptibility genes were amplified and sequenced. Variations were detected predicting a novel missense mutation (V110I) in KCNQ1, as well as a common polymorphism in KCNH2 (K897T). We expressed wild-type (WT) or V110I Kv7.1 channels in CHO-K1 cells cotransfected with KCNE1 and performed patch-clamp analysis. In addition, WT or K897T Kv11.1 were also studied by patch clamp. Current-voltage (I-V) relations for V110I showed a significant reduction in both developing and tail current densities compared with WT at potentials >+20 mV (p < 0.05; n = 8 cells, each group), suggesting a reduction in IKs currents. K897T- Kv11.1 channels displayed a significantly reduced tail current density compared with WT-Kv11.1 at potentials >+10 mV. Interestingly, channel availability assessed using a triple-pulse protocol was slightly greater for K897T compared with WT (V0.5 = -53.1 ± 1.13 mV and -60.7 ± 1.15 mV for K897T and WT, respectively; p < 0.05). Comparison of the fully activated I-V revealed no difference in the rectification properties between WT and K897T channels. We report a patient with a loss-of-function mutation in KCNQ1 and a loss-of-function polymorphism in KCNH2. Our results suggest that a reduction of both IKr and IKs underlies the combined LQT1 and LQT2 phenotype observed in this patient. |
DOI: | doi:10.1139/Y10-094 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1139/Y10-094 |
| DOI: https://doi.org/10.1139/Y10-094 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Adult |
| Amino Acid Sequence |
| Animals |
| Base Sequence |
| Cells, Cultured |
| CHO Cells |
| Cricetinae |
| Cricetulus |
| Electrocardiography |
| ERG1 Potassium Channel |
| Ether-A-Go-Go Potassium Channels |
| Female |
| Genetic Variation |
| Humans |
| KCNQ1 Potassium Channel |
| Long QT Syndrome |
| Molecular Sequence Data |
| Mutation |
| Phenotype |
| Polymorphism, Genetic |
K10plus-PPN: | 1850471088 |
Verknüpfungen: | → Zeitschrift |
Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2 / Cordeiro, Jonathan M. [VerfasserIn]; 1 December 2010 (Online-Ressource)