Novel Genomic Approach to the Arrhytmogenic Sudden Cardiac Death

Abstract

Unfortunately, most of the common diseases in cardiology do not show traditional Mendelian genetics, they usually are complex genetic diseases resulting from the combination of multiple heritable and environmental factors. However, one of the cardiology dysfunction that can affect apparently healthy young adults or with any previous heart disease, such as sudden cardiac death (SCD), could be the first symptom of a Mendelian disease such as cardiomyopathies or channelopathies. In many of the SCD cases, especially in case of young people, the cause of death cannot be explained neither after autopsy nor after laboratory tests. Inherited heart diseases such as hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and primary electrical diseases such as long QT syndrome (LQTS), Brugada syndrome (BrS) or catecholaminergic polymorphic ventricular tachycardia (CPVT), are the main cause of death in young adults with no previous clinical history. Most often these inherited cardiac disorders give rise to lethal ventricular arrhythmias and show an autosomal dominant mode of inheritance. Genetic screening of the genes described as implicated in the different pathologies may help to determine the cause of death and to evaluate the potential risk of the relatives. Today we know which are the main causes of sudden cardiac death in young adults and we also know which are the genes responsible of these diseases in a high percentage of cases. The aim of this article is to present to the reader the estate of the art of the use of the new next generation sequencing technologies for the study of arrhythmogenic sudden cardiac deaths. We will discuss the different available technologies, and the different applications: Candidate gene resequencing. We will describe the interesting genes to be studied and the different strategies available for their enrichment and sequencing Whole exome resequencing. We will describe the application of this approach to those cases were we need to look for new genes.