The added value of the Greek National Network of Precision Medicine in Cardiology. Greece is a natural park of rare diseases

Abstract Background The Greek National Network of Precision Medicine in Cardiology consists of a consortium of public sector hospitals, forensic services and genetic testing institutes. Aim This network aims to prevent sudden death in young people and study hereditary cardiovascular diseases in Greece. Method Two large national registries have been established, one for patients with hereditary heart diseases and one for sudden deaths in young people. A National Registration Platform has been created. Those registries lead to the evaluation of families with hereditary diseases or with sudden death in young people and to the identification of people within the families who suffer from hereditary cardiovascular disease (CV) and are not aware of it. At the same time, it identifies areas of the country with clusters of inherited CV diseases. Results Within the framework of the network, as a pilot project, we present the results of our own hospital which has tested 2.500 patients with inherited heart diseases and has performed 316 genetic tests on patients diagnosed with hereditary disease. Of the 316 patients, 42 tested positive for pathogenic (P) genetic variation, 74 positive for a likely pathogenic (LP) variant, and 72 for variant of unknown significance. The percentage of genes with the detected variants is shown in Figure 1. Out of the 116 families with P/LP variants, 88 families had at least the proband tested at our center and an average of 2.5 family members were also screened. From 233 screened relatives of probands with P/LP variants, 149 (64%) were found positive for the proband's variant. Clinical evaluation revealed typical or subclinical disease in 35% of the relatives, while 29% of them were phenotype negative. At the same time, areas with a founder effect phenomenon were identified in the country, specifically in Crete hypertrophic cardiomyopathy (HCM) and ATTR inherited amyloidosis, Attica (HCM), Central Greece (PLN cardiomyopathy) and the Cyclades (Naxos disease-JUP cardiomyopathy). Also nests of rare hereditary diseases such as Cohen disease in Fourni of Ikaria and Wilson disease in Kalymnos, as well as areas of the Peloponnese and the island of Ios with neuromuscular diseases that also have cardiovascular involvement. Conclusion Greece, due to its islands and isolated areas, is a natural park of rare cardiovascular diseases. The Greek National Network of Precision Medicine in Cardiology constitutes an added value for the country's health services by identifying areas that need special interventions as well as populations that we have not been able to identify until now.Genetic profile of patients