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Status: Bibliographieeintrag

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Verfasst von:Cordeiro, Jonathan M. [VerfasserIn]   i
 Perez, Guillermo J. [VerfasserIn]   i
 Schmitt, Nicole [VerfasserIn]   i
 Pfeiffer, Ryan [VerfasserIn]   i
 Nesterenko, Vladislav V. [VerfasserIn]   i
 Burashnikov, Elena [VerfasserIn]   i
 Veltmann, Christian [VerfasserIn]   i
 Borggrefe, Martin [VerfasserIn]   i
 Wolpert, Christian [VerfasserIn]   i
 Schimpf, Rainer [VerfasserIn]   i
 Antzelevitch, Charles [VerfasserIn]   i
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

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