RBM20 – Hypertrophic Cardiomyopathy

Heterozygous rare variants in RBM20 have been implicated in a large case-control study of 793 hypertrophic cardiomyopathy (HCM) patients and 414 healthy controls. Gene-based association analysis using SKAT-O demonstrated a significant enrichment of RBM20 rare variants in HCM cases, implicating RBM20 as a susceptibility gene for HCM (PMID:34333030). RBM20 heterozygotes exhibited a higher prevalence of sudden cardiac arrest (6.7% vs 0.9%, P = 0.001) (PMID:34333030), increased sudden cardiac death risk factors, impaired left ventricular systolic function, and greater incidences of resuscitated cardiac arrest, nonsustained ventricular tachycardia, and malignant arrhythmias.

Mendelian randomization suggested that RBM20 expression in the left ventricle is causally associated with HCM, indicating opposing effects on HCM and dilated cardiomyopathy (PMID:34333030). However, no familial segregation data or functional assays specific to HCM have been reported, limiting the current evidence.

Key take-home: RBM20 rare variants may contribute to HCM susceptibility and arrhythmogenic risk, supporting the inclusion of RBM20 in genetic testing panels pending further validation.

References

• The Canadian journal of cardiology | 2021 | RBM20 Is a Candidate Gene for Hypertrophic Cardiomyopathy PMID:34333030

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