Challenges of genetics in the diagnosis of sudden cardiac death. Interest of forensic and legal medicine.

Sudden cardiac death is the leading cause of death in developed countries and a small but significant number of cases cannot be explained after a thorough autopsy process. Cases of sudden cardiac death in people under 40years of age are mainly due to structural heart disease or cardiomyopathies and arrhythmogenic diseases or channelopathies. In these cases, the search for associated genetic factors through molecular autopsy may help to find the cause of unexplained sudden cardiac death, through genetic diagnosis of previously undiagnosed channelopathies or cardiomyopathies.

Prevalence and relevance of H558R in the efficacy and toxicity of flecainide in patients with atrial fibrillation: a cohort study.

Background: The SCN5A gene polymorphism histidine-558-to-arginine (H558R) has been associated with atrial fibrillation (AF) and may affect the therapeutic effects of flecainide. This study aimed to assess the prevalence of the H558R polymorphism in a European cohort of patients with AF and examine its association with flecainide's effects on AF recurrence and toxicity.

Methods: This cohort study included patients diagnosed with AF and prescribed flecainide between 2017 and 2021 in a regional health area.

Meta-analysis of genome-wide association studies for cancer therapy-related cardiovascular dysfunction and functional mapping highlight an intergenic region close to TP63.

Cancer therapy-related cardiac dysfunction (CTRCD), which commonly includes left ventricular dysfunction and heart failure, is the main adverse effect of anticancer therapy. In recent years several candidate genes studies and genome-wide association studies have identified common genetic variants associated with CTRCD, but evidence remains limited and few genetic variants are robust. A genome-wide meta-analysis of CTRCD was performed with 852 oncology patients receiving cancer therapy.

Detection of the Copy Number Variants of Genes in Patients with Familial Cardiac Diseases by Massively Parallel Sequencing.

Introduction: The implication of copy number variations in familial heart disease is known, although in-depth knowledge is lacking; hence, more studies are needed to further our understanding. Massively parallel sequencing, thanks to its recent surge in use, is emerging as a valid tool for the detection of this type of variant, through the use of appropriate software.

Methods: We conducted a study with 182 patients diagnosed with mendelian cardiovascular diseases who underwent sequencing using a cardiac gene panel and then a specific calling process for copy number variations (CNVs) with ExomeDepth software, which provides us with a Bayes factor (BF), a score of the probability that a CNV detected is true.

Searching for genetic modulators of the phenotypic heterogeneity in Brugada syndrome.

In Brugada syndrome, even within the same family where all affected individuals share the same mutation, phenotypic variation is prominent, with variable penetrance and expressivity, presenting different degrees of involvement. It is difficult to establish a direct correlation between genotype and phenotype to predict prognosis in complications and risk of sudden death. The factors that modulate this inter- and intra-familial phenotypic variability remain to be determined.