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

The <i>GPD1L</i> 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 p...

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Main Authors: Andrea Greco, Estefanía Martínez-Barrios, José Cruzalegui, Sergi Cesar, Fredy Chipa, Nuria Díez-Escuté, Patricia Cerralbo, Irene Zschaeck, Paula Loredo, Georgia Sarquella-Brugada, Oscar Campuzano
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Language:English
Published: MDPI AG 2025-03-01
Series:Cardiogenetics
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Online Access:https://www.mdpi.com/2035-8148/15/1/9
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author Andrea Greco
Estefanía Martínez-Barrios
José Cruzalegui
Sergi Cesar
Fredy Chipa
Nuria Díez-Escuté
Patricia Cerralbo
Irene Zschaeck
Paula Loredo
Georgia Sarquella-Brugada
Oscar Campuzano
author_facet Andrea Greco
Estefanía Martínez-Barrios
José Cruzalegui
Sergi Cesar
Fredy Chipa
Nuria Díez-Escuté
Patricia Cerralbo
Irene Zschaeck
Paula Loredo
Georgia Sarquella-Brugada
Oscar Campuzano
author_sort Andrea Greco
collection DOAJ
description The <i>GPD1L</i> 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 <i>GPD1L</i> 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 <i>GPD1L</i> 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 <i>GPD1L</i> gene as a cause of Brugada syndrome. In summary, to date, there is insufficient evidence to conclude a definitive association between <i>GPD1L</i> and Brugada syndrome.
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series Cardiogenetics
spelling doaj-art-c9a73a5b006141abb6785a18bce6fa352025-08-20T02:11:18ZengMDPI AGCardiogenetics2035-82532035-81482025-03-01151910.3390/cardiogenetics15010009Brugada Syndrome and <i>GPD1L</i>: Definite Genotype-Phenotype Association?Andrea Greco0Estefanía Martínez-Barrios1José Cruzalegui2Sergi Cesar3Fredy Chipa4Nuria Díez-Escuté5Patricia Cerralbo6Irene Zschaeck7Paula Loredo8Georgia Sarquella-Brugada9Oscar Campuzano10Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainArrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainArrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainArrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainArrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainArrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainArrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainArrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainArrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainArrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, SpainMedical Science Department, School of Medicine, Universitat de Girona, 17003 Girona, SpainThe <i>GPD1L</i> 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 <i>GPD1L</i> 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 <i>GPD1L</i> 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 <i>GPD1L</i> gene as a cause of Brugada syndrome. In summary, to date, there is insufficient evidence to conclude a definitive association between <i>GPD1L</i> and Brugada syndrome.https://www.mdpi.com/2035-8148/15/1/9arrhythmiasBrugada syndrome<i>GPD1L</i>geneticsreinterpretation
spellingShingle Andrea Greco
Estefanía Martínez-Barrios
José Cruzalegui
Sergi Cesar
Fredy Chipa
Nuria Díez-Escuté
Patricia Cerralbo
Irene Zschaeck
Paula Loredo
Georgia Sarquella-Brugada
Oscar Campuzano
Brugada Syndrome and <i>GPD1L</i>: Definite Genotype-Phenotype Association?
Cardiogenetics
arrhythmias
Brugada syndrome
<i>GPD1L</i>
genetics
reinterpretation
title Brugada Syndrome and <i>GPD1L</i>: Definite Genotype-Phenotype Association?
title_full Brugada Syndrome and <i>GPD1L</i>: Definite Genotype-Phenotype Association?
title_fullStr Brugada Syndrome and <i>GPD1L</i>: Definite Genotype-Phenotype Association?
title_full_unstemmed Brugada Syndrome and <i>GPD1L</i>: Definite Genotype-Phenotype Association?
title_short Brugada Syndrome and <i>GPD1L</i>: Definite Genotype-Phenotype Association?
title_sort brugada syndrome and i gpd1l i definite genotype phenotype association
topic arrhythmias
Brugada syndrome
<i>GPD1L</i>
genetics
reinterpretation
url https://www.mdpi.com/2035-8148/15/1/9
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