English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

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

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.

Item is

Basic

show hide
Genre: Journal Article
Alternative Title : Biophysical characterization of KCNQ1 P320 mutations linked to long QT syndrome 1

Files

show Files
hide Files
:
JMolCellCardiol_48_2010_230.pdf (Any fulltext), 2MB
 
File Permalink:
-
Name:
JMolCellCardiol_48_2010_230.pdf
Description:
-
OA-Status:
Visibility:
Restricted (Max Planck Institute for Medical Research, MHMF; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Creators

show
hide
 Creators:
Thomas, Dierk, Author
Khalil, Markus, Author
Alter, Markus, Author
Schweizer, Patrick1, 2, Author           
Karle, Christoph A., Author
Wimmer, Anna-Britt, Author
Licka, Manuela, Author
Katus, Hugo A., Author
Koenen, Michael1, 2, Author           
Ulmer, Herbert E., Author
Zehelein, Joerg2, Author           
Affiliations:
1Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              
2Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

Content

show
hide
Free keywords: Genetic testing; Ion channels; KCNQ1 delayed rectifier potassium channel; Long QT syndrome; Sudden cardiac death
 Abstract: 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.

Details

show
hide
Language(s): eng - English
 Dates: 2009-05-062009-06-122009-06-212010-01-01
 Publication Status: Issued
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 664716
DOI: 10.1016/j.yjmcc.2009.06.009
URI: http://www.ncbi.nlm.nih.gov/pubmed/19540844
Other: 7482
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Molecular and Cellular Cardiology (London)
  Other : J. Mol. Cell. Cardiol.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London : Academic Press
Pages: - Volume / Issue: 48 (1) Sequence Number: - Start / End Page: 230 - 237 Identifier: ISSN: 0022-2828
CoNE: https://pure.mpg.de/cone/journals/resource/954922646041