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  Identification and characterisation of a novel KCNQ1 mutation in a family with Romano-Ward syndrome

Zehelein, J., Thomas, D., Khalil, M., Wimmer, A.-B., Koenen, M., Licka, M., et al. (2004). Identification and characterisation of a novel KCNQ1 mutation in a family with Romano-Ward syndrome. Biochimica et Biophysica Acta, 1690(3), 185-192. doi:10.1016/j.bbadis.2004.06.024.

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Genre: Journal Article
Alternative Title : Identification and characterisation of a novel KCNQ1 mutation in a family with Romano-Ward syndrome

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 Creators:
Zehelein, Joerg1, Author              
Thomas, Dierck, Author
Khalil, Markus, Author
Wimmer, Anna-Britt, Author
Koenen, Michael1, 2, Author              
Licka, Manuela, Author
Wu, K., Author
Kiehn, J., Author
Brockmeier, Konrad, Author
Kreye, V. A., Author
Karle, Christoph A., Author
Katus, Hugo A., Author
Ulmer, Herbert E., Author
Schoels, Wolfgang, Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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Free keywords: IKs current; KCNQ1 (KVLQT1); Long QT syndrome; Electrophysiology; Mutation
 Abstract: Romano-Ward syndrome (RWS), the autosomal dominant form of the congenital long QT syndrome, is characterised by prolongation of the cardiac repolarisation process associated with ventricular tachyarrhythmias of the torsades de pointes type. Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be responsible for this disorder. Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequence analysis have identified a KCNQ1 mutation in a family that were clinically conspicuous due to several syncopes and prolonged QTc intervals in the ECG. The mutant subunit was expressed and functionally characterised in the Xenopus oocyte expression system. A novel heterozygous missense mutation with a C to T transition at the first position of codon 343 (CCA) of the KCNQ1 gene was identified in three concerned family members (QTc intervals: 500, 510 and 530 ms, respectively). As a result, proline 343 localised within the highly conserved transmembrane segment S6 of the KCNQ1 channel is replaced by a serine. Co-expression of mutant (KCNQ1-P343S) and wild-type (KCNQ1) cRNA in Xenopus oocytes produced potassium currents reduced by approximately 92%, while IKs reconstitution experiments with a combination of KCNQ1 mutant, wild-type and KCNE1 subunits yielded currents reduced by approximately 60%. A novel mutation (P343S) identified in the KCNQ1 subunit gene of three members of a RWS family showed a dominant-negative effect on native IKs currents leading to prolongation of the heart repolarisation and possibly increases the risk of malign arrhythmias with sudden cardiac death.

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Language(s): eng - English
 Dates: 2004-06-162004-02-172004-06-162004-08-032004-11-05
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Biochimica et Biophysica Acta
Source Genre: Journal
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Publ. Info: Amsterdam [etc.] : Elsevier
Pages: - Volume / Issue: 1690 (3) Sequence Number: - Start / End Page: 185 - 192 Identifier: ISSN: 0006-3002
CoNE: https://pure.mpg.de/cone/journals/resource/954925384085