Introduction: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a rare tachyarrhythmia typically presenting with bidirectional ventricular tachycardia, appearing during physical or emotional stress. Mutations in the Ryanodine receptor gene RYR2 are known to cause an autosomal dominant type of the disease (CPVT1). As part of our effort to elucidate the molecular basis of cardiac anomalies, we studied the genetic basis of CPVT in a consanguineous family with healthy parents and two siblings presenting with a diagnosis of CPVT.
Methods: We obtained thorough family history, complete patients` phenotype including: ECG, stress tests, echocardiography, and performed Whole Exome Sequencing analysis.
Results: A nineteen years old asymptomatic male presented with cardiac arrest during physical stress. While visiting him in the intensive care unit, his thirteen years old sister experienced major emotional stress, and suffered from cardiac arrest as well. Thorough family workup including ECG, stress test and echocardiography, revealed asymptomatic parents and siblings, one of which was found to have multifocal premature ventricular contractions during stress test. Echocardiography for all family members revealed normal cardiac anatomy. The three affected members underwent implantable cardiac defibrillator implantation and received metoprolol therapy.
Whole Exome Sequencing identified homozygous Gly3118Arg missense mutation in the RYR2 gene. The mutation segregated with the phenotype in the family: The affected members were homozygous for the mutation whereas the non-affected parents and siblings were heterozygous. The mutation is located in the cytosolic component of the RYR2 protein.
Conclusion: This is a first report of autosomal recessive CPVT1 caused by homozygous RYR2 mutation.
