Biomedical Research

Newly Discovered Gene Mutant Reveals New Mechanisms for Heart Failure

Recent research on genetic heart disease has revealed information regarding heart failure. A newly discovered gene mutant known as RBM20 affects the way dilated cardiomyopathy is connected to heart failure.


Dilated cardiomyopathy is a disease of the heart muscle where the ventricle of the heart stretches and dilates and can’t pump blood as well, usually starting in the left ventricle of the heart. While the cause of dilated cardiomyopathy often can’t be determined, numerous factors can cause the left ventricle to dilate and weaken, including diabetes, obesity, hypertension, alcohol abuse, certain cancer medications, cocaine use and abuse, infections, including those caused by bacteria, viruses, fungi, and parasites, exposure to toxins, such as lead, mercury, and cobalt, arrhythmias and complications of late-stage pregnancy. Ultimately, poor blood flow from the left ventricle can lead to heart failure. Additionally, enlargement of the left ventricle may make it harder for your heart valves to close, causing a backward flow of blood and making your heart pump less effectively. Dilated cardiomyopathy can also cause your heart to suddenly stop beating. 

Figure 1: This figure shows an illustration of a normal heart versus a heart affected by dilated cardiomyopathy. The differences are clear that a heart affected with dilated cardiomyopathy has thickened walls due to the enlargement of the left ventricle. 

About ten years ago, a pediatric cardiologist at Mayo Clinic, had traced this disease to a genetic mutation in a gene known as RBM20. This gene causes cardiomyopathy to affect patients ages as early as young adulthood. 

Analysis of Research and Study

Although in the past ten years, heart failure in the RBM20 form of cardiomyopathy was connected to the abnormal splicing of genes for proteins that help the heart’s muscles contract, the new research suggests that the mutant RBM20 actually damages the heart muscle cells. The damage is done through the buildup of pathological ribonucleoprotein granules which end up harming everything inside the healthy cells. This causes the formation of the new version of dilated cardiomyopathy. Dr. Tim Nelson MD, Ph.D., who is the research study lead author and director, and his team had created the first-ever large animal model. Their model was of a pig that was born with the human gene RBM20 for dilated cardiomyopathy. Their model includes a display of all the signs and symptoms of heart failure. Within months, the large animal model had allowed them to further look into the gene and study the development of dilated cardiomyopathy where on the contrary it takes more than 20 years for results to show for dilated cardiomyopathy in humans. 

Dr. Nelson and his team had conducted a simple staining test using pig heart tissue samples that contained RNA-binding protein. Their discovery was verified using a similar study conducted one decade ago using tissue samples from Dr. Olson, a pediatric cardiologist at Mayo Clinic, RBM20 dilated cardiomyopathy human patient tissue. 

Dr. Nelson and his team say that it is important to comprehend that there could be young children to adults who may be suffering from dilated cardiomyopathy due to the RBM20 gene mutant. Dr. Nelson says, “We have taken these findings back into the lab and developed cell cultures to test new therapeutics. The future of this research is focused on moving discoveries out of the lab and into clinical trials to make new therapies available to our patients. This research is a very important catalytic step to do that.” (Tim Nelson, MD, Ph.D., Study Lead Author, and Director, Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome, Mayo Clinic). 

Usually, the overload of protein granules in cells happens in the brain or the spinal cord. However, due to this recent discovery, it has now been found that overgrowth of protein granules in cells can also occur in the heart. However, the benefit of this is that the heart is a much larger and more accessible organ compared to the brain tissue or the spinal cord. Dr.Jay Schneider, MD, Ph.D., who is a Mayo Clinic cardiologist and first author of the study conducted says, “[…] we can study and develop therapies to prevent the buildup of these toxic granules at the beginning of life instead of waiting 50 years or more for a degenerative disease to appear clinically. This is a huge advantage that should accelerate drug discovery in ribonucleoprotein granule degenerative diseases of the heart and nervous system.” 


Dilated cardiomyopathy is the most common type of genetic heart disease, occurring mostly in adults 20 to 60. It affects the heart’s ventricles and atria, in the lower and upper chambers of the heart. However, new research shows that the new form of RBM20 dilated cardiomyopathy can also affect young adults and can lead to heart valve problems, arrhythmias, and blood clots in the heart. There is still much to be discovered on this new gene mutant and its effects causing heart failure. 

Samiksha Komatireddy, Youth Medical Journal 2020


[1] Henderson, Reviewed by Emily. “Research on Genetic Heart Disease Uncovers New Mechanism for Heart Failure.” News, 19 Nov. 2020,

[2] Ani. “Cellular Pathway of Genetic Heart Disease Similar to Neurodegenerative Disease: Health.” Devdiscourse, Devdiscourse, 19 Nov. 2020,

[3] “RWJBarnabas Health, Inc.” RWJBarnabas Health,


By Samiksha Komatireddy

Samiksha Komatireddy is a first year undergraduate student majoring in biochemistry on the pre-med track. She is interested in pursuing a career in the medical field, specifically in neurosurgery. She has been interning as a research intern of neurological surgery and health affairs at the University of California, Irvine Medical Center from 2017-present. Samiksha is also an active COVID-19 contact tracer and care navigator for LA county testing sites in Redondo Beach, California.

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