title: DHPLC analysis of potassium ion channel genes in congenital long QT syndrome.
abstract: Congenital long QT syndrome (LQTS) is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). As a result of these arrhythmias, patients suffer from recurrent syncopes, seizures, or sudden death as the most dramatic event. Mutations in five genes, encoding cardiac ion channels, have been identified in LQTS. Two potassium-channel genes, KCNQ1 (LQT1) and KCNH2 (LQT2 or HERG), are frequently involved in LQTS. Potassium-channel defects account for approximately 50-60% of LQTS. As patients benefit from preventive medication, early detection of a genetic defect is desired to identify the family members at risk. Speed and sensitivity of mutation detection was improved by applying the denaturing high performance liquid chromatography (DHPLC) technique for analysis of the entire KCNQ1 and KCNH2 genes and the protein encoding part of the KCNE1 and KCNE2 genes. By using this methodology, seven missense mutations in the KCNQ1 gene and nine mutations (four missense, two nonsense, one insertion, and two deletions) in the KCNH2 gene have been identified in a total number of 32 index patients diagnosed with LQTS syndrome. We conclude that this method is suitable for rapid identification of LQT gene defects due to the combination of automation, high throughput, sensitivity, and short time of analysis.
authors.affiliation: Department of Genetics and Cell Biology, University Maastricht, Maastricht, The Netherlands. roselie.jongbloed@gen.unimaas.nl
authors.forename: Roselie
authors.initials: R
authors.lastname: Jongbloed
authors.forename: Carlo
authors.initials: C
authors.lastname: Marcelis
authors.forename: Crool
authors.initials: C
authors.lastname: Velter
authors.forename: Pieter
authors.initials: P
authors.lastname: Doevendans
authors.forename: Joep
authors.initials: J
authors.lastname: Geraedts
authors.forename: Hubert
authors.initials: H
authors.lastname: Smeets
mesh_terms: D001483:Base Sequence; D027682:Cation Transport Proteins; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods*; D051638:Ether-A-Go-Go Potassium Channels; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009691:Nucleic Acid Denaturation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated
chemical_list: D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk)