Genetic and Clinical Characterization of a South-Brazilian Hypertrophic Cardiomyopathy Cohort

Le résumé fourni par la source

Abstract Background Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease, characterized by genetic and phenotypic heterogeneity. Although extensively studied in North American and European populations, data from Brazil remain limited. Objectives To characterize the genetic and clinical profiles of a Southern Brazilian cohort of HCM patients and their relatives using massive parallel sequencing. Methods In this observational study, HCM patients and first-degree relatives were recruited from outpatient cardiology clinics. Clinical and imaging data were collected, and genetic analysis used a 100-gene panel. Variant pathogenicity was assessed according to American College of Medical Genetics and Genomics criteria, and statistical analyses were performed using R software. Results Eighty individuals were included in the final analysis (mean age: 49.2 ±18.5); 60% male; 40 index cases and 40 affected relatives). MYH7 and MYBPC3 were the most frequently related genes, with pathogenic / likely pathogenic variants (P/LP) identified in 33% and 16% of participants, respectively. No pathogenic TNNT2 variants were detected. Ninety percent of participants carried an identified variant (including variants of uncertain significance), with 68% harboring P/LP variants. MYH7 carriers exhibited a higher proportion of left ventricular outflow tract obstruction, whereas MYBPC3 carriers had a higher proportion of arrhythmic events and earlier diagnosis; however, these differences did not reach statistical significance and should be interpreted as exploratory. Clinical comparisons revealed regional differences, suggesting the potential impact of genetic diversity on the presentation of HCM in this part of Brazil. Conclusions This study offers the first detailed genetic and clinical characterization of a Brazilian HCM cohort using massive parallel sequencing. Our findings underscore the importance of genetic testing for diagnosis, risk stratification, and management.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.