TRIM63 Gene Identified as Key Factor in Common Heart Disease, Offering New Hope for Early Detection

Recent research conducted by scientists at the Clalit Research Institute has uncovered the significant role of the TRIM63 gene in hypertrophic cardiomyopathy (HCM), the most prevalent inherited heart disorder worldwide. Published in Circulation: Genomic and Precision Medicine, the study highlights how mutations in TRIM63 contribute to disease development and susceptibility.

Led by Dr. Noa Ruhrman Shahar from Rabin Medical Center and Professor Shay Ben-Shachar, the research analyzed 107 unrelated HCM patients from diverse backgrounds, including Ashkenazi Jews, Muslim Arabs, and Middle Eastern Jewish communities. The findings revealed that 4.7% of these patients carried biallelic (two copies) pathogenic variants in TRIM63. These individuals experienced early-onset, severe thickening of heart muscle, frequent arrhythmias, and fainting episodes, with some requiring implantable defibrillators before diagnosis.

In addition, 7.5% of patients had monoallelic (single copy) pathogenic variants. These variants were found 8.2 times more often in HCM patients than in control groups, indicating that even a single faulty TRIM63 gene significantly increases the risk of developing the disease.

An especially noteworthy discovery was a mutation (c.277C>T) prevalent among individuals of Libyan Jewish descent, estimated to occur in 1 in 14,400 people, underscoring the importance of targeted genetic screening in isolated or consanguineous populations.

This breakthrough has important clinical implications. Recognizing and screening for TRIM63 mutations could enable earlier diagnosis and intervention, significantly reducing the risk of severe cardiac events. Despite its importance, TRIM63 has often been omitted from commercial HCM gene panels due to previous uncertainties about its role. This study underscores the need to incorporate TRIM63 into genetic screening protocols, especially with the advantages offered by exome-based testing, which allows for ongoing reanalysis as new genetic data emerge.

Incorporating TRIM63 into routine testing could lead to more accurate diagnoses, personalized treatment plans, and improved outcomes for patients and their families. As Prof. Ben-Shachar highlights, understanding the gene's role opens new opportunities for prevention and tailored care in heart disease, with potential benefits for millions globally.

This research marks a significant advancement in cardiac genetics, emphasizing the critical importance of genetic testing in detecting high-risk individuals early and guiding effective clinical management.

Source: https://medicalxpress.com/news/2025-04-trim63-key-gene-common-heart.html