Work

Autosomal recessive hypertrophic cardiomyopathy associated with variants in TRIM63

Year: 2025

Type: article

Abstract: Background Hypertrophic cardiomyopathy (HCM) is typically linked to dominant variants in sarcomeric genes, but rare minor genes, including TRIM63 coding for an E3 ubiquitin-protein ligase, have recently emerged as potential causes of recessive HCM. Methods and results Among 517 adult patients with clinical HCM who underwent next-generation sequencing, we found six index cases carrying biallelic TRIM63 variants—four homozygous and two compound heterozygous. They presented with early-onset disease, marked concentric hypertrophy, diffuse myocardial fibrosis, and progressive left ventricular dysfunction. One patient underwent heart transplantation. No cardiac disease was found in heterozygous relatives. Conclusions TRIM63 -related HCM is rare but clinically distinct. Early identification of TRIM63 homozygous and two compound heterozygous variants in HCM is crucial and warrants proactive clinical surveillance. Take home messages: •TRIM63-related HCM is a rare autosomal-recessive subtype with early onset and severe phenotypes. •Rapid disease progression is common, with extensive fibrosis and frequent transition to hypokinetic-dilated end-stage cardiomyopathy. •Early genetic diagnosis supports proactive management, including timely ICD implantation for arrhythmia risk and reproductive counselling for families due to the recessive inheritance.

Source: International Journal of Cardiology

DOI: 10.1016/j.ijcard.2025.134010