Abstract
Dilated cardiomyopathy (DCM) is a progressive disease of heart muscle characterized by chamber enlargement and wall dilatation, resulting in reduced systolic function. DCM is the most common form of nonischemic cardiomyopathy, and up to 30% of cases are estimated to be familial in nature.1 The majority of identified causative genes encode proteins responsible for muscle contraction or cellular architecture, yet DCM genes may be quite functionally distinct. An intriguing example is RBM20 , which encodes RNA-binding motif protein 20 (RBM20), a pre-mRNA splicing factor that is highly expressed in striated muscle, particularly the heart.2 Genetic association between DCM and this post-transcriptional RNA processing protein was established in 2009 when missense mutations from 2 large families with autosomal-dominant DCM were mapped to RBM20 . Subsequent profiling of a large cohort of idiopathic DCM patients identified additional missense mutations, all of which cluster within an arginine/serine–rich protein domain between amino acids 634 and 638.3 RBM20-dependent DCM (CMD1DD, OMIM #613172) occurs in ≈3% of DCM patients,4 and disease pathology recapitulated in RBM20 loss-of-function and deletion models involves altered splicing of numerous genes, including several linked to cardiomyopathy, ion transport, and contractile function.2,5,6 Presumably, these splice variants are directly regulated by RBM20 activity; however, TTN remains the only validated direct mRNA target.2 In a recent study in the …
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.