Deutsch
 
Benutzerhandbuch Datenschutzhinweis Impressum Kontakt
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

Biophysical characterization of KCNQ1 P320 mutations linked to long QT syndrome 1

MPG-Autoren
/persons/resource/persons95266

Schweizer,  Patrick
Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society;
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons93829

Koenen,  Michael
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;
Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons96072

Zehelein,  Joerg
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Thomas, D., Khalil, M., Alter, M., Schweizer, P., Karle, C. A., Wimmer, A.-B., et al. (2010). Biophysical characterization of KCNQ1 P320 mutations linked to long QT syndrome 1. Journal of Molecular and Cellular Cardiology (London), 48(1), 230-237. doi:10.1016/j.yjmcc.2009.06.009.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002C-5E7F-8
Zusammenfassung
Hereditary long QT syndrome (LQTS) is a cardiovascular disorder characterized by prolongation of the QT interval on the surface ECG and a high risk for arrhythmia-related sudden death. Mutations in a cardiac voltage-gated potassium channel, KCNQ1, account for the most common form of LQTS, LQTS1. The objective of this study was the characterization of a novel KCNQ1 mutation linked to LQTS. Electrophysiological properties and clinical features were determined and compared to characteristics of a different mutation at the same position. Single-strand conformation polymorphism analysis followed by direct sequencing was performed to screen LQTS genes for mutations. A novel missense mutation in the KCNQ1 gene, KCNQ1 P320H, was identified in the index patient presenting with recurrent syncope and aborted sudden death triggered by physical stress and swimming. Electrophysiological analyses of KCNQ1 P320H and the previously reported KCNQ1 P320A mutation indicate that both channels are non-functional and suppress wild type I(Ks) in a dominant-negative fashion. Based on homology modeling of the KCNQ1 channel pore region, we speculate that the proline residue at position 320 limits flexibility of the outer pore and is required to maintain the functional architecture of the selectivity filter/pore helix arrangement. Our observations on the KCNQ1 P320H mutation are consistent with previous studies indicating that pore mutations in potassium channel alpha-subunits are associated with more severe electrophysiological and clinical phenotypes than mutations in other regions of these proteins. This study emphasizes the significance of mutation screening for diagnosis, risk-assessment, and mutation-site specific management in LQTS patients.