PO104 The Greek National Network of Precision Medicine in Cardiology (GR i-Cardiac Net): single center genetic data from probands and family screening

Abstract Background The Greek national network of precision medicine in Cardiology (GR i-Cardiac Net) aims to prevent sudden death in the young and study hereditary cardiovascular diseases (CV) in Greece. It involves university and public sector hospitals, forensic services and genetic testing institutes. Methods Two large national registries have been established, one for patients with hereditary CV and one for sudden death in young people. A National Registration Platform has been created. Those registries led to the evaluation of families with hereditary CV or history of sudden death at young age and to the identification of affected family members. At the same time, this network identified areas of the country with clusters and nests of inherited CV. Results Within the framework of the network, we present the results of the coordinating center which has tested 3222 patients (2019-2022) with inherited CV and performed 435 genetic tests on patients diagnosed with these diseases. Out of these 435 patients, 128 (29. 4%) were tested positive for a pathogenic (P) /likely pathogenic (LP) variant, while in 100 (22. 9%) probands a Variant of Uncertain Significance (VUS) was identified. The percentage of genes with the detected variants in the probands is shown in Figure 1. Out of 128 families with P/LP variant, an average of 2. 5 family members were screened. From 320 screened relatives of probands with P/LP variants, 175 (54. 6%) were found positive for the proband’s variant. At the same time, areas with a founder effect phenomenon were identified in the country, specifically in Crete and Attica (hypertrophic cardiomyopathy, MYBPC3 c. 3784₃795del and MYH7 c. 1063GA), in Central Greece PLN cardiomyopathy, PLN c. 116TG, p. (Leu39*) and in Cyclades (Naxos disease- JUP cardiomyopathy, JUP c. 2038₂039delTG p. Trp680Glyfs). Also nests of rare hereditary diseases such as Cohen disease in Ikaria island, Wilson disease in Kalymnos island, ATTR inherited amyloidosis in Crete and neuromuscular diseases with cardiovascular involvement in Peloponnese and the island of Ios were identified. Conclusions The national network of precision medicine in cardiology constitutes an added value for the country’s health services by creating clinical-genetic maps of hereditary CV, identifying affected family members and highlighting populations in specific geographic areas that need special interventions. Greece, due to its islands and isolated areas, is a natural park of rare cardiovascular diseases.