New gene discovery could transform screening and treatment for heart disease

A groundbreaking discovery from Israeli scientists is changing what doctors know about inherited heart disease. Researchers have pinpointed a gene, TRIM63, as a major contributor to hypertrophic cardiomyopathy (HCM), the most common inherited heart condition around the world.

These findings, published in Circulation: Genomic and Precision Medicine, promise to reshape how people are screened and treated for this dangerous disease.

The study was led by Dr. Noa Ruhrman Shahar of Rabin Medical Center (Beilinson Hospital) and Professor Shay Ben-Shachar of the Clalit Research Institute. Their work strengthens the evidence that TRIM63 not only causes HCM but also greatly increases a person's risk of developing it.

“This is a life-saving discovery,” said Dr. Ruhrman Shahar. “Recognizing carriers of disease-causing TRIM63 mutations enables early monitoring and intervention, dramatically lowering the risk of severe, even fatal, cardiac events.”

In a detailed analysis, the team studied 107 unrelated patients diagnosed with HCM. They used advanced exome-based gene panels, a method that captures a wide range of genetic information. Patients came from diverse backgrounds, including Ashkenazi Jews, Muslim Arabs, and North African and Middle Eastern Jewish communities.

The results revealed that about 4.7% of these patients carried two faulty copies of the TRIM63 gene, a situation known as biallelic mutation. This group represented 18.5% of all those who received a genetic diagnosis during the study. These individuals developed heart muscle thickening at an early age, experienced frequent arrhythmias, and suffered from repeated fainting spells. Some even needed implantable cardioverter defibrillators before doctors knew their condition was genetic.

Additionally, the researchers found that 7.5% of the patients carried only one faulty copy of the gene. When compared to a group of people without heart disease, these single-copy carriers were 8.2 times more likely to have HCM. This strongly suggested that even having one bad copy of TRIM63 puts people at high risk.

An unexpected finding was a mutation called c.277C>T, previously unknown to scientists. It showed up in several patients of Libyan Jewish descent. The team estimated the disease frequency for this group at about one in 14,400 individuals. The discovery points to the importance of targeted genetic screening in specific populations where marrying within the community is common.

“These findings provide vital new insight,” said Professor Ben-Shachar. “Beyond advancing our scientific understanding, they offer a real opportunity to prevent complications in thousands of high-risk patients through personalized care.”

Even though early studies hinted that TRIM63 might play a role in heart disease, it has not been routinely included in commercial HCM gene panels. This was mainly because scientists were not completely sure about its importance.

The new research removes much of that doubt. It provides strong evidence that TRIM63 needs to be part of genetic screening, especially for groups already shown to carry higher risks. Including TRIM63 would not only help spot cases earlier but also help tailor treatment to each person's specific needs.

The study also showcased the benefits of exome-based genetic testing over older methods. Exome testing allows doctors to keep updating their analysis as new genetic links are discovered. Traditional gene-specific panels can quickly become outdated, missing critical information like the connection to TRIM63.

Adding TRIM63 to standard HCM testing could lead to important improvements in medical care. Doctors could diagnose patients earlier and offer special surveillance for family members who might also carry risky genes. Treatment plans could then be personalized based on each person's exact genetic profile.

All of these changes could lead to better clinical outcomes, reducing hospitalizations, emergency procedures, and sudden cardiac deaths. Patients could live longer and healthier lives with fewer complications.

The success of this study was possible because of a broad collaboration across Israel. It drew on resources from the Clalit Research Institute and Rabin Medical Center, among others. The work was supported by Clalit Health Services, the largest healthcare provider in Israel. Clalit’s genomic database, one of the country’s most diverse, was essential to identifying the TRIM63 connection.

The project also benefited from the Berkowitz Family Living Laboratory, a partnership between Clalit and Harvard Medical School’s Department of Biomedical Informatics. This program uses artificial intelligence and data science to advance healthcare worldwide.

“Our findings represent a major step forward in cardiac genetics,” said Dr. Ruhrman Shahar. “This mutation causes severe cardiomyopathy and should be recognized as a key risk factor for heart dysfunction. We believe these insights will impact millions worldwide, both in diagnosis and in care.”

The discovery of TRIM63’s role in HCM offers a clear message: early detection saves lives. Genetic testing that includes this gene can lead to faster action, smarter treatment plans, and hope for countless families facing a hidden threat.

Thanks to innovative research and powerful collaborations, heart disease may no longer have the upper hand. With TRIM63 in the spotlight, doctors have a new tool to protect the hearts of future generations.

Note: The article above provided above by The Brighter Side of News.

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