Brugada Syndrome and <i>GPD1L</i>: Definite Genotype-Phenotype Association?

Abstract

The GPD1L gene encodes a small cytoplasmic protein that is involved in the regulation of sodium currents. Alterations in this gene have been associated with Brugada syndrome. This rare arrhythmogenic syndrome is characterized by a typical electrocardiographic pattern, incomplete penetrance, variable expressivity, and risk of sudden cardiac death. To date, few families with a clinical diagnosis of Brugada syndrome caused by a rare alteration in the GPD1L gene have been reported worldwide. The increase in data focused on genetic variants allows us to improve the interpretation of their role in Brugada syndrome. In our study, we have compiled the GPD1L variants reported so far in patients with a definitive clinical diagnosis or suspected Brugada syndrome. We performed an exhaustive update and interpretation of each variant following the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Our results showed that none of the variants described to date can be classified as truly harmful in Brugada syndrome. Despite this fact, more clinical and genetic data are needed to definitively rule out the GPD1L gene as a cause of Brugada syndrome. In summary, to date, there is insufficient evidence to conclude a definitive association between GPD1L and Brugada syndrome.

Keywords

• arrhythmias
• Brugada syndrome
• <i>GPD1L</i>
• genetics
• reinterpretation