Autosomal recessive hypertrophic cardiomyopathy associated with variants in TRIM63.

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.