Our experience in genetic heart disease

Brugada syndrome is one of the main focuses of the clinical and research activity of our Cardiogenetics Service. To date, over 300 families with Brugada syndrome have been studied, for a total of about 1,000 patients, including probands and family members.

In addition to Brugada syndrome, our service has studied over 200 families carrying arrhythmic heart diseases of probable genetic origin, in particular long QT syndrome and arrhythmogenic right ventricular dysplasia (ARVD).

In the case of probands with a suspicion of Brugada Syndrome, in our center, the genetic screening is carried out through the NGS method on a panel of 25 genes (ABCC9, AKAP9, CACNA1C, CACNA2D1, CACNB2, DSC, DSG2, GPD1L, HCN4, KCND2 , KCND3, KCNE3, KCNE5, KCNH2, KCNJ8, MOG1, PKP2, RANGRF, SCN5A, SCN10A, SCN1B, SCN2B, SCN3B, SEMA3A, TRPM4).

Since 2018, there is also a research protocol that offers patients with the diagnosis of Brugada syndrome an in-depth analysis with experimental analysis of the entire DNA (WGS analysis).

According to data from the literature, genetic analysis for Brugada syndrome enables molecular confirmation of the condition in 30% of cases (Gene Reviews, 2019). The percentage of cases confirmed by our service is higher, reaching 45% (unpublished data).

In patients in whom a mutation is discovered, about 50% have a variant in SCN5A, a gene involved in the function of the sodium channel, while the remaining cases present with anomalies in at least one of the other genes analyzed. In this regard, research conducted by our service has enabled the clarification of a relevant role played by the SCN10A gene in the pathogenesis of Brugada syndrome.