Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited 
arrhythmogenic disease so far related to mutations in the cardiac ryanodine 
receptor (RYR2) or the cardiac calsequestrin (CASQ2) genes. Because mutations in 
RYR2 or in CASQ2 are not retrieved in all CPVT cases, we searched for mutations 
in the physiological protein partners of RyR2 and CSQ2 in a large cohort of CPVT 
patients with no detected mutation in these two genes. Based on a candidate gene 
approach, we focused our investigations on triadin and junctin, two proteins 
that link RyR2 and CSQ2. Mutations in the triadin (TRDN) and in the junctin 
(ASPH) genes were searched in a cohort of 97 CPVT patients. We identified three 
mutations in triadin which cosegregated with the disease on a recessive mode of 
transmission in two families, but no mutation was found in junctin. Two TRDN 
mutations, a 4 bp deletion and a nonsense mutation, resulted in premature stop 
codons; the third mutation, a p.T59R missense mutation, was further studied. 
Expression of the p.T59R mutant in COS-7 cells resulted in intracellular 
retention and degradation of the mutant protein. This was confirmed after in 
vivo expression of the mutant triadin in triadin knock-out mice by viral 
transduction. In this work, we identified TRDN as a new gene responsible for an 
autosomal recessive form of CPVT. The mutations identified in the two families 
lead to the absence of the protein, thereby demonstrating the importance of 
triadin for the normal function of the cardiac calcium release complex in 
humans.