Identification of novel mutations in RBM20 in patients with dilated cardiomyopathy

Clin Transl Sci. 2010 Jun;3(3):90-7. doi: 10.1111/j.1752-8062.2010.00198.x.


The genetic basis of most of dilated cardiomyopathy (DCM) cases remains unknown. A recent study indicated that mutations in a highly localized five amino acid hotspot in exon 9 of RBM20, a gene encoding a ribonucleic acid-binding protein, caused aggressive DCM. We undertook this study to confi rm and extend the nature of RBM20 mutations in another DCM cohort. Clinical cardiovascular data, family histories, and blood samples were collected from patients with idiopathic DCM. DNA from 312 DCM probands was sequenced for nucleotide alterations in exons 6 through 9 of RBM20, and additional family members as possible. We found six unique RBM20 rare variants in six unrelated probands (1.9%). Four mutations, two of which were novel (R634W and R636C) and two previously identified (R634Q and R636H), were identified in a five amino acid hotspot in exon 6. Two other novel variants (V535I in exon 6 and R716Q in exon 9) were outside of this hotspot. Age of onset and severity of heart failure were variable, as were arrhythmias and conduction system defects, but many subjects suffered severe heart failure resulting in early death or cardiac transplantation. This article concludes that DCM in patients with RBM20 mutations is associated with advanced disease.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Base Sequence
  • Cardiomyopathy, Dilated / genetics*
  • Child
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Pedigree
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics*
  • Young Adult


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