CAV3 – Brugada Syndrome

Caveolin-3 (CAV3) has been investigated in Brugada syndrome (BrS) cohorts due to its role in ion channel scaffolding and membrane microdomain organization. In a Danish and Iranian SCN5A-negative BrS cohort of 42 patients, comprehensive Sanger sequencing of CAV3 revealed no pathogenic variants (PMID:22284586). Similarly, next-generation sequencing of 28 arrhythmia-associated genes in 45 additional SCN5A-negative BrS probands identified no rare CAV3 variants above population frequency (PMID:26230511). No familial segregation of CAV3 alleles with BrS phenotype has been reported, and functional studies to date have not demonstrated CAV3 perturbations that would recapitulate the BrS ECG pattern or arrhythmogenic substrate.

Given the absence of reproducible genetic findings or mechanistic data linking CAV3 disruption to Brugada syndrome, the association is categorized as Limited. There is currently no justification for including CAV3 in clinical BrS genetic testing panels. Future studies may explore non-coding or deep-intronic regions, but clinical utility remains unsupported.

References

• The Canadian journal of cardiology • 2012 • Sodium current and potassium transient outward current genes in Brugada syndrome: screening and bioinformatics. PMID:22284586
• PloS one • 2015 • Genetic Analysis of Arrhythmogenic Diseases in the Era of NGS: The Complexity of Clinical Decision-Making in Brugada Syndrome. PMID:26230511

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