Background: Long QT syndrome is a congenital abnormality of cardiac repolarization causing syncope and sudden death from ventricular tachyarrhythmias known as torsades de pointes. This hereditary cardiac disorder often shows an increase of the value of the QT interval corrected for heart rate over 0.45 s in a 12-lead electrocardiogram.
Objective: To find and identify pertinent mutations occurring in French Canadians by extracting genomic DNA from blood samples and performing a combination of polymerase chain reaction (PCR), single-strand conformational polymorphism and DNA sequencing.
Results: A novel mutation was identified in the S5 region of the HERG potassium channel. In codon 564 CTA, T was replaced by C, resulting in a leucine to proline substitution. Two family members had the mutation in two distinct generations. A new restriction site was created at this position and therefore enabled the development of a rapid diagnostic test using PCR. HERG wild type and mutant potassium channel mRNAs were then expressed in Xenopus laevis oocytes.
Conclusion: This electrophysiological study suggests that coexpression of HERG wild type and mutant L564P results in a dominant negative effect of the mutation.