Caracterització de variants de significat incert situades al gen codificant pel canal de sodi cardíac en cèl·lules HEK-293T

Abstract

Sudden cardiac death is defined as a natural and unexpected death due to cardiac causes, and is responsable for more than 60% of deaths caused by cardiovascular reasons. Brugada syndrome (BrS) is a channelopathy that can lead to sudden cardiac death, and can be caused by variants in the SCN5A gene, which encodes for the cardiac sodium channel (NaV1.5). In this final degree thesis we have studied the possible effect of the variants of uncertain significance SCN5A_c.2302A>G and SCN5A_c.2332 C>T, found in patients with BrS, using HEK-293T cells as a cellular model. It has been observed that both variants decrease the expression of NaV1.5 and modify its localization. This study is very initial and it would be convenient to perform more experiments, but this work shows the importance of the nucleotide conservation of this region of NaV1.5