| Analysis of the human KCNH2(HERG) gene: identification and characterization of a novel mutation Y667X associated with long QT syndrome and a non-pathological 9 bp insertion. | |
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MedLine Citation:
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PMID: 10790218 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Long QT (LQT) syndrome is a potentially life-threatening disorder, characterized by a distinct cardiac arrhythmia known as torsades de pointes. Mutations within a number of genes linked to the familial form, including that coding for a cardiac potassium channel called KCNH2 (HERG), have been described based on the characterized genomic organization. A standardized method was developed to screen the entire gene for gene variants. We report a single base pair substitution, introducing a premature STOP codon at codon 667 of the gene in a healthy individual with an extended QTc interval (460 msec). In vitro expression of the codon Y667X variant in Xenopus oocyte suggests that the autosomal dominant variant does not function in a dominant/negative manner and cannot co-assemble to form a channel, resulting in a reduction of the KCNH2 current, and an extension of the QT interval. This indicates that pathogenic LQT gene variants exist in the apparently normal population, the prognosis and clinical consequences of which remain to be determined. The assays described should facilitate future studies into this area. |
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Authors:
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A Paulussen; P Yang; M Pangalos; P Verhasselt; R Marrannes; C Verfaille; I Vandenberk; R Crabbe; F Konings; W Luyten; M Armstrong |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Human mutation Volume: 15 ISSN: 1098-1004 ISO Abbreviation: Hum. Mutat. Publication Date: 2000 May |
Date Detail:
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Created Date: 2000-09-21 Completed Date: 2000-09-21 Revised Date: 2008-10-28 |
Medline Journal Info:
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Nlm Unique ID: 9215429 Medline TA: Hum Mutat Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 483 Citation Subset: IM |
Copyright Information:
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Copyright 2000 Wiley-Liss, Inc. |
Affiliation:
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Department of Pharmacogenomics, Janssen Research Foundation, Janssen Pharmaceutica, Belgium. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cation Transport Proteins* Codon / genetics DNA-Binding Proteins* Electrophysiology Ether-A-Go-Go Potassium Channels Humans Long QT Syndrome / genetics* Mutagenesis, Insertional / genetics* Patch-Clamp Techniques Potassium Channels / genetics*, physiology Potassium Channels, Voltage-Gated* Trans-Activators* Xenopus laevis / genetics |
| Chemical | |
Reg. No./Substance:
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0/Cation Transport Proteins; 0/Codon; 0/DNA-Binding Proteins; 0/ERG protein, human; 0/ERG1 potassium channel; 0/Ether-A-Go-Go Potassium Channels; 0/KCNH6 protein, human; 0/Potassium Channels; 0/Potassium Channels, Voltage-Gated; 0/Trans-Activators |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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