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Autosomal recessive hypertrophic cardiomyopathy associated with variants in TRIM63

F Bonanni1, A Ballerini2, A Gozzini2

  • 1Cardiology Unit, Meyer Children's Hospital IRCCS, Florence, Italy; Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, Pisa, Italy.

International Journal of Cardiology
|November 7, 2025
PubMed

Insights

Recessive hypertrophic cardiomyopathy (HCM) can be caused by rare TRIM63 gene variants. Identifying these biallelic TRIM63 variants is crucial for early diagnosis and proactive clinical surveillance in affected individuals.

Area of Science:

  • Cardiology
  • Genetics
  • Molecular Biology

Background:

  • Hypertrophic cardiomyopathy (HCM) is predominantly associated with dominant variants in sarcomeric genes.
  • Rare genes, such as TRIM63, are emerging as potential causes of recessive HCM.
  • TRIM63 encodes an E3 ubiquitin-protein ligase involved in protein degradation pathways.

Purpose of the Study:

  • To investigate the role of TRIM63 variants in the etiology of hypertrophic cardiomyopathy.
  • To identify patients with recessive HCM caused by biallelic TRIM63 mutations.
  • To characterize the clinical phenotype associated with TRIM63-related HCM.

Main Methods:

  • Next-generation sequencing was performed on 517 adult patients with clinical HCM.
  • Analysis focused on identifying biallelic variants in the TRIM63 gene.
  • Clinical data, including disease onset, cardiac morphology, fibrosis, and ventricular function, were reviewed.

Main Results:

  • Six index cases with biallelic TRIM63 variants (four homozygous, two compound heterozygous) were identified among 517 patients.
  • TRIM63-related HCM presented with early onset, marked concentric hypertrophy, diffuse myocardial fibrosis, and progressive left ventricular dysfunction.
  • No cardiac disease was observed in heterozygous relatives, suggesting a recessive inheritance pattern.

Conclusions:

  • TRIM63-related hypertrophic cardiomyopathy is a rare but clinically distinct entity.
  • Early identification of biallelic TRIM63 variants is essential for accurate diagnosis.
  • Proactive clinical surveillance is warranted for individuals identified with TRIM63-related HCM.
Abstract

Keywords:
Autosomal recessiveGenetic testingHypertrophic cardiomyopathyMinor genesTRIM63 gene

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