# Case Report: Genomic and clinical insights into MYBPC3-related hypertrophic cardiomyopathy in Ecuadorian patients: implications for sudden cardiac death risk

## TL;DR

This case report explores MYBPC3-related hypertrophic cardiomyopathy in Ecuadorian patients, emphasizing the need for genomic testing in underrepresented populations to better assess sudden cardiac death risk.

## Contribution

The study provides genomic and clinical insights into HCM in Ecuadorian patients, highlighting novel MYBPC3 variants and the importance of genomic testing in admixed populations.

## Key findings

- Three unrelated Ecuadorian patients with HCM were found to have MYBPC3 variants, including likely pathogenic and novel missense mutations.
- Ancestry analysis revealed a mix of Native American, European, and African backgrounds in the Ecuadorian patients.
- Incidental variants in other genes were identified but not directly linked to HCM.

## Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a leading cause of sudden cardiac death (SCD) in young adults and athletes. It exhibits marked clinical variability, which may be influenced by genetic background and environmental factors. Although MYBPC3 is the most frequently implicated gene, data from Latin American and admixed populations remain scarce. In this study, we describe three unrelated Ecuadorian patients with clinically diagnosed HCM who harbored MYBPC3 variants. Two patients carried likely pathogenic mutations (p.Glu258Lys and p.His875Profs*8), while novel missense variants (p.Ala536Pro and p.Thr274Met) were identified as variants of uncertain significance (VUS). Additional variants were detected in TTN, MYLK2, RYR1, SDHA, APOB, and JPH2, but given their classification as VUS or a lack of association with HCM, they are described only as incidental findings. An ancestry analysis revealed heterogeneous contributions of Native American, European, and African backgrounds, reflecting the admixed composition of the Ecuadorian population. This case series underscores the phenotypic heterogeneity of HCM, even among patients with MYBPC3 variants, and highlights the importance of genomic testing in underrepresented populations to improve diagnosis, family screening, and SCD risk stratification.