Role of genetic testing in young patients with idiopathic atrioventricular conduction disease

Auricchio, Angelo; Demarchi, Andrea; Özkartal, Tardu; Campanale, Daniela; Caputo, Maria Luce; Valentino, Marcello Di; Menafoglio, Andrea; Regoli, François; Facchini, Marco; Bufalo, Alessandro Del; Foglia, Pietro E. G.; Ferrari, Nicola; Bomio, Fulvio; Medeiros-Domingo, Argelia; Moccetti, Tiziano; Pedrazzini, Giovanni; Klersy, Catherine; Conte, Giulio

doi:10.1093/europace/euac196

Cited by 7 publications

(2 citation statements)

References 25 publications

(28 reference statements)

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“…Variants in the TRPM4 channel have also been found in BrS patients. This channel, like HCN4 , appears to be involved in the diastolic depolarization that leads to the AP in the sinoatrial node [ 55 , 77 ]. Interestingly, both gain-of-function and loss-of-function TRPM4 variants have been reported in BrS patients, indicating that further studies are required to clarify the role of this channel in the disease [ 58 ].…”

Section: Genetics and Molecular Mechanismsmentioning

confidence: 99%

Brugada Syndrome: More than a Monogenic Channelopathy

Liantonio,

Bertini,

Mele

et al. 2023

Biomedicines

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Brugada syndrome (BrS) is an inherited cardiac channelopathy first diagnosed in 1992 but still considered a challenging disease in terms of diagnosis, arrhythmia risk prediction, pathophysiology and management. Despite about 20% of individuals carrying pathogenic variants in the SCN5A gene, the identification of a polygenic origin for BrS and the potential role of common genetic variants provide the basis for applying polygenic risk scores for individual risk prediction. The pathophysiological mechanisms are still unclear, and the initial thinking of this syndrome as a primary electrical disease is evolving towards a partly structural disease. This review focuses on the main scientific advancements in the identification of biomarkers for diagnosis, risk stratification, pathophysiology and therapy of BrS. A comprehensive model that integrates clinical and genetic factors, comorbidities, age and gender, and perhaps environmental influences may provide the opportunity to enhance patients’ quality of life and improve the therapeutic approach.

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Section: Genetics and Molecular Mechanismsmentioning

confidence: 99%

Brugada Syndrome: More than a Monogenic Channelopathy

Liantonio,

Bertini,

Mele

et al. 2023

Biomedicines

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“…However, idiopathic CCD in adults younger than 50 years is a very rare condition with an incidence of 0.7 per 100 000 persons/year. 45 …”

Section: Cardiac Conduction Defects and Sick Sinus Syndromementioning

confidence: 99%

From gene-discovery to gene-tailored clinical management: 25 years of research in channelopathies and cardiomyopathies

Crotti,

Brugada,

Calkins

et al. 2023

Europace

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In the early nineties, few years before the birth of Europace, the clinical and scientific world of familial arrhythmogenic conditions was revolutionized by the identification of the first disease-causing genes. The explosion of genetic studies over a 15-year period led to the discovery of major disease-causing genes in practically all channelopathies and cardiomyopathies, bringing insight into the pathophysiological mechanisms of these conditions. The birth of next generation sequencing allowed a further step forward and other significant genes, as CALM1–3 in channelopathies and FLN C and TTN in cardiomyopathies were identified. Genotype–phenotype studies allowed the implementation of the genetic results in diagnosis, risk stratification, and therapeutic management with a different level of evidence in different arrhythmogenic conditions. The influence of common genetic variants, i.e. SNPs, on disease manifestation was proved in mid-twenties, and in the last 10 years with the advent of genome-wide association studies performed in familial arrhythmogenic diseases, the concept of polygenic risk score has been consolidated. Now, we are at the start of another amazing phase, i.e. the initiation of first gene therapy clinical trials.

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