AUTHOR=Monasky Michelle M. , Micaglio Emanuele , Ciconte Giuseppe , Benedetti Sara , Di Resta Chiara , Vicedomini Gabriele , Borrelli Valeria , Ghiroldi Andrea , Piccoli Marco , Anastasia Luigi , Santinelli Vincenzo , Ferrari Maurizio , Pappone Carlo TITLE=Genotype/Phenotype Relationship in a Consanguineal Family With Brugada Syndrome Harboring the R1632C Missense Variant in the SCN5A Gene JOURNAL=Frontiers in Physiology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.00666 DOI=10.3389/fphys.2019.00666 ISSN=1664-042X ABSTRACT=

Brugada syndrome (BrS) is a known cause of sudden cardiac death. The genetic basis of BrS is not well understood, and no one single gene is linked to even a majority of BrS cases. However, mutations in the gene SCN5A are the most common, although the high amount of phenotypic variability prevents a clear correlation between genotype and phenotype. Research techniques are limited, as most BrS cases still remain without a genetic diagnosis, thus impairing the implementation of experimental models representative of a general pathogenetic mechanism. In the present study, we report the largest family to-date with the segregation of the heterozygous variant NM_198056:c.4894C>T (p.Arg1632Cys) in the SCN5A gene. The genotype-phenotype relationship observed suggests a likely pathogenic effect of this variant. Functional studies to better understand the molecular effects of this variant are warranted.