Subsequently, we screened for RYR2 mutations (in the 48 critical exons) DNA samples from 18 patients for whom a precise diagnosis had not been obtained, but who had effort-induced polymorphic ventricular arrhythmias as a main symptom.
RYR2 mutations have been reported to be associated with effort-induced polymorphic ventricular arrhythmias, syncope, and sudden death (5-10).
For individuals carrying a pathogenic RYR2 mutation, sudden death is a real risk; fortunately, beta-blocker therapy is effective in most cases (6).
Unfortunately, DHPLC can be successfully applied to only 48 of 53 critical RYR2 exons because of unfavorable nucleotide composition in some amplicons.
In the present study, performed on 22 isolated individuals with effort-induced polymorphic ventricular arrhythmias, we detected four putative pathogenic RYR2 mutations among 48 critical RYR2 exons suitable for DHPLC analysis.
However, all four novel RYR2 mutations reported here involve highly conserved amino acids and map to functionally important regions of the channel, such as the FKBP12.
Thirteen SNPs were detected by DHPLC in RYR2 amplicons from patients considered in this study.
Therefore, in patients with effort-induced polymorphic ventricular arrhythmias, the entire RYR2 gene should be screened for mutations.
DHPLC Detection of RYR2 Mutations receptor/Ca(2+)-release channels from cardiac muscle.