Clinical interpretation of genetic variants in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiac entity characterized by right ventricular, or biventricular, fibrofatty replacement of myocardium. Structural alterations may lead to sudden cardiac death, mainly in young males during exercise. Autosomal dominant pattern of inheritance is reported in most parts of pathogenic genetic variations identified. Currently, 13 genes have been associated with the disease but nearly 40 % of clinically diagnosed cases remain without a genetic diagnosis. New genetic technologies allow further genetic analysis, generating a significant amount of genetic data in novel genes, which is often classified as of ambiguous significance. We focus on genetic advances of arrhythmogenic right ventricular cardiomyopathy, helping clinicians to interpret and translate genetic data into clinical practice

Computer simulation of charge trapping and ballistic deficit effects on gamma-ray spectra from CdTe semiconductor detectors

In recent years, a variety of special-purpose software has been developed to simulate gamma-ray semiconductor detector and associated electronics performances. Unfortunately, these software systems often lack flexibility and cannot be applied outside rather limited ranges. General radiation transport Monte Carlo codes such as ITS and EGS4 can achieve high levels of physical accuracy, but the simulated pulse;height spectra are completely noise free, and therefore differ significantly from experimental results. In this work, the ITS output files have been modified, so as to add to Monte Carlo simulated spectra the subsequent degradation effects inherent in the detection process. Ballistic deficit losses, electronic noise, charge trapping and detrapping are taken into account: the corresponding simulation algorithms are independently combined into the final spectra. As the charge collection efficiency depends upon the position of gamma-ray interactions within the bulk, the detector has been virtually sliced into a large number of sections so as to statistically evaluate the spectrum distortion on a local spectra basis. Although the algorithms developed were applied to gamma-ray spectra obtained from CdTe detectors only, the generality of the method makes it suitable for any semiconductor detector

Genetic and forensic implications in epilepsy and cardiac arrhythmias. a case series

Epilepsy affects approximately 3 % of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17 % of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24 % of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy

Genetics of arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy is a rare clinical entity characterised by fibro-fatty replacement of myocardium, mainly involving right ventricular free wall, leading to malignant electrical instability and sudden cardiac death. The disease is inherited in up to 50% of cases, with incomplete penetrance and variable phenotypic expression. To date, more than 300 pathogenic mutations have been identified in 12 genes, mainly with autosomal dominant inheritance. Here, we focus on recent advances in the genetics of arrhythmogenic right ventricular cardiomyopathy. Despite continuous improvements, current genotype-phenotype studies have not contributed yet to establish a genetic risk stratification of the disease