From gene-discovery to gene-tailored clinical management: 25 years of research in channelopathies and cardiomyopathies
Year: 2023
Type: article
Abstract: In the early nineties, few years before the birth of Europace, the clinical and scientific world of familial arrhythmogenic conditions was revolutionized by the identification of the first disease-causing genes. The explosion of genetic studies over a 15-year period led to the discovery of major disease-causing genes in practically all channelopathies and cardiomyopathies, bringing insight into the pathophysiological mechanisms of these conditions. The birth of next generation sequencing allowed a further step forward and other significant genes, as CALM1-3 in channelopathies and FLN C and TTN in cardiomyopathies were identified. Genotype-phenotype studies allowed the implementation of the genetic results in diagnosis, risk stratification, and therapeutic management with a different level of evidence in different arrhythmogenic conditions. The influence of common genetic variants, i.e. SNPs, on disease manifestation was proved in mid-twenties, and in the last 10 years with the advent of genome-wide association studies performed in familial arrhythmogenic diseases, the concept of polygenic risk score has been consolidated. Now, we are at the start of another amazing phase, i.e. the initiation of first gene therapy clinical trials.
Source: EP Europace
Institutions: IRCCS Istituto Auxologico Italiano, University of Milano-Bicocca, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Johns Hopkins University, Johns Hopkins Medicine, Lyon 1 Université, Hospices Civils de Lyon, Institut NeuroMyoGène, Ente Ospedaliero Cantonale, Istituto Cardiocentro Ticino, St George's, University of London, Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam, Centre National de la Recherche Scientifique, Inserm, Centre Hospitalier Universitaire de Nantes, Institut du Thorax, Nantes Université, St George’s University Hospitals NHS Foundation Trust
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,518
Awards: G2184034017, G7087147045
OpenAlex ID: W4386154309