1. ¹Department of Medicine and Biomedicum Helsinki, Helsinki, Finland
2. ²Department of Cardiology, University of Helsinki, Helsinki, Finland

Correspondence: Dr K Kontula, Department of Medicine, University of Helsinki, Haartmaninkatu 4, FIN-00290, Helsinki, Finland. Tel: 358 9 4717 2230; Fax: 358 9 4717 4013; E-mail: kimmo.kontula@hus.fi

Received 18 March 2003; Revised 2 June 2003; Accepted 10 June 2003.

Abstract

Mutations of two myocardial calcium signaling molecules, ryanodine receptor 2 (RYR2) and calsequestrin 2 (CASQ2), may cause catecholaminergic polymorphic ventricular tachycardia (CPVT), a severe inherited arrhythmic disease manifesting with salvoes of exercise-induced bidirectional and polymorphic tachycardias. We screened 12 Finnish CPVT probands for mutations in these genes and identified three novel RYR2 mutations (V2306I, P4902L, R4959Q), which were absent in unaffected and control individuals. Although no obvious disease-causing mutations were identified in the CASQ2 gene, the molecular screening revealed two novel amino-acid polymorphisms (T66A and V76M). The frequencies of these polymorphisms in 185 unrelated probands with long QT syndrome and in 280 healthy blood donors were not significantly different. These data, combined with our previous findings, show that RYR2 mutations are present in at least 6/16 (38%) of the catecholaminergic polymorphic ventricular tachycardia families, while CASQ2 mutations must be a rare cause of CPVT.