RBM20 Truncating Variants and Human Cardiomyopathy - PubMed
3 hours ago
- #RBM20 variants
- #cardiomyopathy
- #genetic diagnosis
- RBM20 truncating variants (RBM20tvs) have an unclear role in arrhythmogenic dilated cardiomyopathy (DCM), unlike pathogenic/likely pathogenic (P/LP) missense variants.
- The study assessed RBM20 variants in UK Biobank and All of Us populations, finding an etiologic fraction of 0.53 for arrhythmogenic DCM.
- Individuals with RBM20 variants had a lower lifetime incidence of cardiomyopathy, heart failure, or major ventricular arrhythmia compared to those with titin truncating variants (TTNtvs).
- Patients with RBM20tvs presented later in life (mean 53 years) than those with P/LP RBM20 variants (mean 34 years) and had less family history of cardiac events.
- No significant difference in major heart failure or arrhythmia events was found between RBM20tv and P/LP RBM20 groups after adjustment, but lifetime hazard was reduced for RBM20tvs.
- RBM20 variants contribute to arrhythmogenic DCM but with reduced penetrance compared to TTNtvs and milder severity than P/LP RBM20 variants, suggesting potential additive effects with other variants.