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Case Reports
. 2022 Feb 22:13:743472.
doi: 10.3389/fgene.2022.743472. eCollection 2022.

Case Report: Two New Cases of Autosomal-Recessive Hypertrophic Cardiomyopathy Associated With TRIM63-Compound Heterozygous Variant

Sofiya Andreeva  1 , Olga Chumakova  2 , Elena Karelkina  3 , Viktoriya Lebedeva  3 , Tamara Lubimtseva  3 , Andrey Semenov  3 , Alexey Nikitin  4 , Gleb Speshilov  5 , Alexandra Kozyreva  1 , Polina Sokolnikova  1 , Sergey Zhuk  1 , Yuliya Fomicheva  1 , Olga Moiseeva  3 , Anna Kostareva  1   6
Affiliations
Case Reports

Case Report: Two New Cases of Autosomal-Recessive Hypertrophic Cardiomyopathy Associated With TRIM63-Compound Heterozygous Variant

Sofiya Andreeva et al. Front Genet. .

Abstract

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary diseases, and it is associated with fatal complications. The clinical heterogeneity of HCM requires risk prediction models to identify patients at a high risk of adverse events. Most HCM cases are caused by mutations in genes encoding sarcomere proteins. However, HCM is associated with rare genetic variants with limited data about its clinical course and prognosis, and existing risk prediction models are not validated for such patients' cohorts. TRIM63 is one of the rare genes recently described as a cause of HCM with autosomal-recessive inheritance. Herein, we present two cases of HCM associated with TRIM63-compound heterozygous variants in young male sportsmen. They demonstrated progressively marked hypertrophy, advanced diastolic dysfunction, a significant degree of fibrosis detected by magnetic resonance imaging, and clear indications for implantable cardioverter-defibrillator. One of the cases includes the first description of TRIM63-HCM with extreme hypertrophy. The presented cases are discussed in light of molecular consequences that might underlie cardiac and muscle phenotype in patients with mutations of TRIM63, the master regulator of striated muscle mass.

Keywords: MuRF1; TRIM63; compound heterozygote; diastolic dysfunction; extreme hypertrophy; hypertrophic cardiomyopathy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Instrumental findings in Patient 1. Electrocardiogram (A) and echocardiography picture correspondence to four-chamber (B) view and long-axis view (C) illustrated severe hypertrophy. Сardiac MRI images in the short (D) and long (E) axes, demonstrating wall hypertrophy, limited cavity volume, and late gadolinium enhancement (F,G).
FIGURE 2
FIGURE 2
Instrumental findings of Patient 2. Electrocardiogram demonstrates voltage criteria of left ventricle hypertrophy and secondary repolarization changes (A). Echocardiogram correspondence to four-chamber (B) and long-axis view (C) and MRI images in the long (D) and short-axis view (E) confirm wall hypertrophy. Arrows indicate the late gadolinium enhancement phenomenon (F,G) in the basal anteroseptal segment.
FIGURE 3
FIGURE 3
Sequencing data and pedigree of Patient 1 (A,B) and Patient 2 (C,D).
See this image and copyright information in PMC

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