RBM20 Is a Candidate Gene for Hypertrophic Cardiomyopathy

Can J Cardiol. 2021 Nov;37(11):1751-1759. doi: 10.1016/j.cjca.2021.07.014. Epub 2021 Jul 29.


Background: The genetic basis of a considerable fraction of hypertrophic cardiomyopathy (HCM) cases remains unknown. Whether the gene encoding RNA binding motif protein 20 (RBM20) is implicated in HCM and the correlation of clinical characteristics of RBM20 heterozygotes with HCM remain unresolved. We aimed to investigate the association between RBM20 variants and HCM.

Methods: We compared rare variants in the RBM20 gene by exome sequencing in 793 patients with HCM and 414 healthy controls. Based on a case-control approach, we used optimal sequence kernel association test (SKAT-O) to explore whether RBM20 is associated with HCM. The genetic distribution of RBM20 rare variants was then compared between HCM heterozygotes and dilated cardiomyopathy (DCM) heterozygotes. Clinical features and prognosis of RBM20 heterozygotes were compared with nonheterozygotes.

Results: Gene-based association analysis implicated RBM20 as a susceptibility gene for developing HCM. Patients with RBM20 variants displayed a higher prevalence of sudden cardiac arrest (SCA) (6.7% vs 0.9%, P = 0.001), increased sudden cardiac death (SCD) risk factor counts and impaired left ventricle systolic function. Further survival analysis revealed that RBM20 heterozygotes had higher incidences of resuscitated cardiac arrest, recurrent nonsustained ventricular tachycardia, and malignant arrhythmias. Mendelian randomization suggested that RBM20 expression in the left ventricle was causally associated with HCM and DCM with opposite effects.

Conclusions: This study identified RBM20 as a potential causal gene of HCM. RBM20 variants are associated with increased risk for SCA in HCM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathy, Hypertrophic / diagnosis
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / metabolism
  • DNA / genetics*
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Genetic Association Studies / methods*
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Humans
  • Magnetic Resonance Imaging, Cine
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Phenotype
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Retrospective Studies


  • RNA-Binding Proteins
  • ribonucleic acid binding motif protein 20, human
  • DNA