Genetic Testing in Brugada Syndrome: A 30-Year Experience-Reference-Cited by-同舟云学术

Genetic Testing in Brugada Syndrome: A 30-Year Experience

Published:2024-04 Issue:4 Volume:17 Page:
ISSN:1941-3149
Container-title:Circulation: Arrhythmia and Electrophysiology
language:en
Short-container-title:Circ: Arrhythmia and Electrophysiology

Author:

Pannone Luigi¹^ORCID,Bisignani Antonio¹^ORCID,Osei Randy²^ORCID,Gauthey Anaïs¹^ORCID,Sorgente Antonio¹^ORCID,Monaco Cinzia¹^ORCID,Della Rocca Domenico Giovanni¹^ORCID,Del Monte Alvise¹^ORCID,Strazdas Antanas¹^ORCID,Mojica Joerelle¹^ORCID,Al Housari Maysam¹^ORCID,Miraglia Vincenzo¹^ORCID,Mouram Sahar¹^ORCID,Vetta Giampaolo¹^ORCID,Paparella Gaetano¹,Ramak Robbert¹^ORCID,Overeinder Ingrid¹,Bala Gezim¹^ORCID,Almorad Alexandre¹^ORCID,Ströker Erwin¹,Pappaert Gudrun¹^ORCID,Sieira Juan¹,de Ravel Thomy²^ORCID,La Meir Mark³^ORCID,Sarkozy Andrea¹^ORCID,Brugada Pedro¹^ORCID,Chierchia Gian Battista¹,Van Dooren Sonia²⁴^ORCID,de Asmundis Carlo¹^ORCID

Affiliation:

1. Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology & Pacing, Universitair Ziekenhuis Brussel – Vrije Universiteit Brussel, European Reference Networks Guard-Heart (L.P., A.B., A.G., A. Sorgente, C.M., D.G.D.R., A.D.M., A.S., J.M., M.A.H., V.M., S.M., G.V., G. Paparella, R.R., I.O., G.B., A.A., E.S., G. Pappaert, J.S., A. Sarkozy, P.B., G.B.C., C.d.A.).

2. Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research Group Reproduction and Genetics, Centre for Medical Genetics (R.O., T.d.R., S.V.D.).

3. Cardiac Surgery Department, Universitair Ziekenhuis Brussel – Vrije Universiteit Brussel (M.L.M.).

4. Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research Group Reproduction and Genetics, Brussels Interuniversity Genomics High Throughput Core (BRIGHTcore), Belgium (S.V.D.).

Abstract

BACKGROUND: A pathogenic/likely pathogenic variant can be found in 20% to 25% of patients with Brugada syndrome (BrS) and a pathogenic/likely pathogenic variant in SCN5A is associated with a worse prognosis. The aim of this study is to define the diagnostic yield of a large gene panel with American College of Medical Genetics and Genomics variant classification and to assess prognosis of SCN5A and non-SCN5A variants. METHODS: All patients with BrS, were prospectively enrolled in the Universitair Ziekenhuis Brussel registry between 1992 and 2022. Inclusion criteria for the study were (1) BrS diagnosis; (2) genetic analysis performed with a large gene panel; (3) classification of variants following American College of Medical Genetics and Genomics guidelines. Patients with a pathogenic/likely pathogenic variant in SCN5A were defined as SCN5A + . Patients with a reported variant in a non-SCN5A gene or with no reported variants were defined as patients with SCN5A − . All variants were classified as missense or predicted loss of function. RESULTS: A total of 500 BrS patients were analyzed. A total of 104 patients (20.8%) were SCN5A + and 396 patients (79.2%) were SCN5A − . A non-SCN5A gene variant was found in 75 patients (15.0%), of whom, 58 patients (77.3%) had a missense variant and 17 patients (22.7%) had a predicted loss of function variant. At a follow-up of 84.0 months, 48 patients (9.6%) experienced a ventricular arrhythmia (VA). Patients without any variant had higher VA-free survival, compared with carriers of a predicted loss of function variant in SCN5A + or non-SCN5A genes. There was no difference in VA-free survival between patients without any variant and missense variant carriers in SCN5A + or non-SCN5A genes. At Cox analysis, SCN5A + or non-SCN5A predicted loss of function variant was an independent predictor of VA. CONCLUSIONS: In a large BrS cohort, the yield for SCN5A + is 20.8%. A predicted loss of function variant carrier is an independent predictor of VA.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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