Update on Genetic Basis of Brugada Syndrome: Monogenic, Polygenic or Oligogenic?

Campuzano, Òscar; Sarquella‐Brugada, Georgia; César, Sergi; Arbelo, Elena; Brugada, Josép; Brugada, Ramón

doi:10.3390/ijms21197155

Cited by 38 publications

(33 citation statements)

References 64 publications

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“…BrS is a complex disease that has been described to have an oligogenic model of inheritance [ 10 , 48 ], and several possible genetic causes have been proposed, reviewed elsewhere [ 10 , 49 ]. It has also been hypothesized that, when people are overstressed by large meals and alcohol, especially during festivities, possible mutations in genes encoding for SULT1A enzymes result in the inability of those enzymes to deactivate catecholamines in the intestine, possibly inducing cardiac arrhythmia [ 50 ].…”

Section: The Mechanisms Behind Food and Alcohol Intake As A Trigger For Brs Ecg Pattern Manifestationmentioning

confidence: 99%

Impact of Dietary Factors on Brugada Syndrome and Long QT Syndrome

et al. 2021

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A healthy regime is fundamental for the prevention of cardiovascular diseases (CVD). In inherited channelopathies, such as Brugada syndrome (BrS) and Long QT syndrome (LQTS), unfortunately, sudden cardiac death could be the first sign for patients affected by these syndromes. Several known factors are used to stratify the risk of developing cardiac arrhythmias, although none are determinative. The risk factors can be affected by adjusting lifestyle habits, such as a particular diet, impacting the risk of arrhythmogenic events and mortality. To date, the importance of understanding the relationship between diet and inherited channelopathies has been underrated. Therefore, we describe herein the effects of dietary factors on the development of arrhythmia in patients affected by BrS and LQTS. Modifying the diet might not be enough to fully prevent arrhythmias, but it can help lower the risk.

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Section: The Mechanisms Behind Food and Alcohol Intake As A Trigger For Brs Ecg Pattern Manifestationmentioning

confidence: 99%

Impact of Dietary Factors on Brugada Syndrome and Long QT Syndrome

et al. 2021

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“…To date, more than 350 rare variants associated with BrS have been described within the SCN5A coding regions [ 108 , 109 ], representing 20–25% of clinically diagnosed BrS cases [ 110 ]. These variants are scattered along the Na V 1.5 protein, which consists of four homologous domains joined by so-called linkers, where each domain contains six transmembrane helices linked by intracellular or extracellular loops.…”

Section: Role Of Scn5a Protein-coding Variantsmentioning

confidence: 99%

Role of Non-Coding Variants in Brugada Syndrome

Pérez-Agustin

Pinsach-Abuin

Pagans

2020

IJMS

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Brugada syndrome (BrS) is an inherited electrical heart disease associated with a high risk of sudden cardiac death (SCD). The genetic characterization of BrS has always been challenging. Although several cardiac ion channel genes have been associated with BrS, SCN5A is the only gene that presents definitive evidence for causality to be used for clinical diagnosis of BrS. However, more than 65% of diagnosed cases cannot be explained by variants in SCN5A or other genes. Therefore, in an important number of BrS cases, the underlying mechanisms are still elusive. Common variants, mostly located in non-coding regions, have emerged as potential modulators of the disease by affecting different regulatory mechanisms, including transcription factors (TFs), three-dimensional organization of the genome, or non-coding RNAs (ncRNAs). These common variants have been hypothesized to modulate the interindividual susceptibility of the disease, which could explain incomplete penetrance of BrS observed within families. Altogether, the study of both common and rare variants in parallel is becoming increasingly important to better understand the genetic basis underlying BrS. In this review, we aim to describe the challenges of studying non-coding variants associated with disease, re-examine the studies that have linked non-coding variants with BrS, and provide further evidence for the relevance of regulatory elements in understanding this cardiac disorder.

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“…It was described to lie on the same spectrum of cardiac electrophysiologic pathology as LQT3, caused by the same variant in SCN5A (5). Today, BrS is considered a Mendelian disorder inherited in an autosomal dominant fashion, even if alternative mechanisms of inheritance have been recently proposed (6). In BrS patients, variants in SCN5A are found more commonly than in any other gene (7) but confirm the clinical diagnosis in only a minority of cases (8).…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Use of Genetics in Brugada Syndrome Risk Stratification

Monasky

Micaglio

Locati

et al. 2021

Front. Cardiovasc. Med.

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The evolution of the current dogma surrounding Brugada syndrome (BrS) has led to a significant debate about the real usefulness of genetic testing in this syndrome. Since BrS is defined by a particular electrocardiogram (ECG) pattern, after ruling out certain possible causes, this disease has come to be defined more for what it is not than for what it is. Extensive research is required to understand the effects of specific individual variants, including modifiers, rather than necessarily grouping together, for example, “all SCN5A variants” when trying to determine genotype-phenotype relationships, because not all variants within a particular gene act similarly. Genetic testing, including whole exome or whole genome testing, and family segregation analysis should always be performed when possible, as this is necessary to advance our understanding of the genetics of this condition. All considered, BrS should no longer be considered a pure autosomal dominant disorder, but an oligogenic condition. Less common patterns of inheritance, such as recessive, X–linked, or mitochondrial may exist. Genetic testing, in our opinion, should not be used for diagnostic purposes. However, variants in SCN5A can have a prognostic value. Patients should be diagnosed and treated per the current guidelines, after an arrhythmologic examination, based on the presence of the specific BrS ECG pattern. The genotype characterization should come in a second stage, particularly in order to guide the familial diagnostic work-up. In families in which an SCN5A pathogenic variant is found, genetic testing could possibly contribute to the prognostic risk stratification.

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Update on Genetic Basis of Brugada Syndrome: Monogenic, Polygenic or Oligogenic?

Cited by 38 publications

References 64 publications

Impact of Dietary Factors on Brugada Syndrome and Long QT Syndrome

Impact of Dietary Factors on Brugada Syndrome and Long QT Syndrome

Role of Non-Coding Variants in Brugada Syndrome

Evaluating the Use of Genetics in Brugada Syndrome Risk Stratification

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