BACKGROUND: The genetic background of catecholaminergic polymorphic ventricular 
tachycardia (CPVT) has been extensively investigated for the last decade in 
Western countries, but it remains unstudied in the Asian population.
METHODS AND RESULTS: In 50 Japanese probands from unrelated families who 
satisfied clinical criteria for CPVT, genetic testing was conducted in all exons 
on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 
(CASQ2) and inward rectifier potassium channel 2 (KCNJ2), and the clinical 
features between RYR2-genotyped and -non-genotyped patient groups were compared. 
Genetic and clinical evaluation was also done in 46 family members. In the 
genetic screening, 28 (18 novel) RYR2 (56.0%), 1 compound heterozygous CASQ2 
(2.0%) and 1 KCNJ2 (2.0%) mutation carriers were identified. In the RYR2 
mutation-positive group, the frequency of bidirectional ventricular tachycardia 
and the use of β-blockers were significantly higher than in the 
mutation-negative group. In contrast, there was no significant difference in 
supraventricular arrhythmias between the 2 groups. With regard to disease 
penetrance, the number of family members of RYR2-genotyped probands with a 
clinical diagnosis of CPVT was high.
CONCLUSIONS: Thirty gene mutation carriers were found for 3 genes in 50 probands 
clinically diagnosed as having CPVT. The penetrance of CPVT phenotype was 
significantly higher in RYR2 mutation carriers, thus RYR2 gene screening in CPVT 
patients would be indispensable to prevent unexpected cardiac sudden death of 
young family members.