Molecular Autopsy of Sudden Cardiac Death: Preliminary Experience of the Northeast Italy Juvenile Sudden Death Registry
E Carturan, G Thiene, C Basso. University of Padua Medical School, Padua, Italy
Background: Molecular genetic screening is currently employed in the clinical diagnostic track of inherited cardiovascular diseases to identify disease-causing mutations. More recently, these techniques have been also applied to sudden death (SD) autopsies which remain unexplained after a thorough post-mortem investigation or in those with inherited cardiomyopathies. The aim of this study was to perform a genetic screening of known disease-causing genes involved in catecholaminergic polymorphic ventricular tachycardia (CPVT) or arrhythmogenic right ventricular cardiomyopathy (ARVC).
Design: Ten cases of juvenile SD (all males, age range 16-35 yrs) from the Veneto Region Registry were investigated. Genetic screening was performed for cardiac ryanodine receptor (RyR2) and calsequestrin (CASQ2) genes in two cases with structural normal heart, and for plakophilin-2 (PKP2), desmoplakin (DSP), desmoglein-2 (DSG2), desmocollin-2 (DSC2) and plakoglobin (JUP) genes in eight cases with ARVC. In five cases the investigation was conducted directly in the proband who died suddenly on frozen autoptic EDTA-blood (3), on frozen tissue (1) or on paraffin-embedded tissue (1). The other five cases were studied indirectly by screening EDTA-blood samples of parents.
Results: The autoptic paraffin embedded tissue was inadequate, whereas frozen autoptic EDTA- blood and frozen tissue were suitable for genetic investigation. Pathogenic gene mutations were identified in five SD cases: in 2 cases in the autopsy probands (one ARVCDSG2-H790Y, one unexplained SD with structurally normal heartRyR2-A2387P), and in the other 3 cases indirectly in the parents (all ARVC: PKP2-G59X, DSP-c.1686+1 C>T, DSG2-V56M). The mutation identified indirectly was discovered in the blood of the mother in two cases and of the father in one. None of these mutation was detected in a 100 genomics DNA (200 chromosomes) from unrelated healthy control subjects from Venetian population.
Conclusions: Molecular autopsy is mandatory on SD cases with structural normal heart as well as in those with inherited structural cardiomyopathies, since it can be potentially life-saving in terms of management and prevention of those left behind. Moreover, it is mandatory that the standard SD autopsy includes archiving either EDTA-preserved blood or frozen tissue to allow postmortem genetic testing.
Tuesday, March 10, 2009 11:00 AM
Platform Session: Section H2, Tuesday Morning