Thursday , November 26 2020

Scientists find eight new unique gene mutations in patients with hereditary heart muscle

In a new study from the Intermountain Healthcare Heart Institute in Salt Lake City, researchers have identified eight new gene mutations that can cause or contribute to idiopathic dilated cardiomyopathy, a form of heart disease that is not due to known external influences such as high blood pressure, obesity, smoking or sick coronary arteries.

For at least 40 percent of these patients, the disease has an underlying genetic cause that causes the muscles in the heart's large pumping chamber (left ventricle) to be too weak and thin to function properly and cause heart failure.

"Although many mutations contributing to non-ischemic dilated cardiomyopathy have been identified, there is still a large gap in our knowledge of its heredity. The more we can learn about what causes the condition, the better we can identify and treat that, "said Jeffrey L. Anderson, MD, research chief and a researcher at the Intermountain Healthcare Heart Institute. "If continued in families, we will be able to identify those at risk of developing heart disease and working to prevent it, diagnose it, and begin treatment earlier."

Results from the study will be presented at the American College of Cardiology Annual Scientific Session in New Orleans on March 18, 2019.

One-fourth to one-third of idiopathic dilated cardiomyopathy patients will need a mechanical support, a heart transplant, or will die within five years, Dr. Anderson, so it's a very serious condition.

In the study, the researchers examined genetic samples of 231 patients with idiopathic dilated cardiomyopathy, evaluated in a special clinic in the Intermountain Medical Center, who voluntarily submitted blood samples in the Intermountain Healthcare INSPIRE Registry and DNA Bank, which is the system's collection of biological samples, clinical information and laboratory consent data. patients diagnosed with a variety of health-related conditions.

In collaboration with Intermountain's Precision Genomics laboratory, researchers sequenced DNA with a focus on the TITIN (TNN) gene encoding the body's largest protein.

"That protein works like a spring in your heart muscle," Dr. said. Anderson. "It improves the muscle's passive elasticity and also limits how much you can stretch it."

Previous studies have already found variants of TTNin patients with idiopathic dilated cardiomyopathy, but history has been incomplete.

Now in this new study, Intermountain researchers identified 24 patients with TTN variants, and eight of these variants had not been seen or documented before. They also confirmed the presence of seven variants that had been discovered and reported previously. The new variants are all of the "truncating" variety, that is, they lead to a shortening of the protein and thus predicted to cause the protein to function in its role of maintaining the integrity of the heart muscle function.

These new variants, Dr. Anderson said will still require functional testing and clinical validation, but they will likely lead to a further expansion of the known spectrum of genes that predispose to idiopathic dilated cardiomyopathy.

The addition of these variants to the current list of known pathological heart muscle protein mutations will help to close the ever-large gap in our knowledge of the resilience of heart muscle diseases and can thus lead to past diagnoses and more effective prevention and treatment.


The study was funded by the Intermountain Foundation and a natural grant from Intermountain Precision Genomics.

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