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

MYH7 and MYBPC3 were the most frequently implicated genes in this South-Brazilian HCM cohort, with pathogenic/likely pathogenic variants identified in 33% and 16% of participants, respectively.

• 80 individuals were included in the final analysis (mean age: 49.2 ± 18.5 years)
• The cohort was 60% male and comprised 40 index cases and 40 affected relatives
• MYH7 P/LP variants were identified in 33% of participants
• MYBPC3 P/LP variants were identified in 16% of participants
• No pathogenic TNNT2 variants were detected in the cohort

The majority of participants carried an identified genetic variant, with 68% harboring pathogenic or likely pathogenic variants.

• 90% of participants carried an identified variant, including variants of uncertain significance (VUS)
• 68% of participants harbored pathogenic/likely pathogenic (P/LP) variants
• Variant pathogenicity was assessed according to American College of Medical Genetics and Genomics (ACMG) criteria
• Genetic analysis used a 100-gene panel via massive parallel sequencing

MYH7 carriers exhibited a higher proportion of left ventricular outflow tract obstruction, while MYBPC3 carriers had a higher proportion of arrhythmic events and earlier diagnosis, though these differences did not reach statistical significance.

• Differences between MYH7 and MYBPC3 carriers in clinical features did not reach statistical significance
• These findings are described as exploratory in nature
• MYH7 carriers showed higher proportion of LVOT obstruction
• MYBPC3 carriers showed higher proportion of arrhythmic events and earlier age at diagnosis

Clinical comparisons revealed regional differences suggesting a potential impact of genetic diversity on the presentation of HCM in Southern Brazil compared to other populations.

• Data from Brazil on HCM genetic and clinical profiles were described as limited prior to this study
• The study is characterized as the first detailed genetic and clinical characterization of a Brazilian HCM cohort using massive parallel sequencing
• Regional differences were identified when comparing findings to North American and European cohorts
• The authors suggest genetic diversity may influence HCM clinical presentation in this region

The study recruited HCM patients and first-degree relatives from outpatient cardiology clinics in Southern Brazil using an observational design.

• Participants were recruited from outpatient cardiology clinics
• Both index cases (n=40) and affected first-degree relatives (n=40) were included
• Clinical and imaging data were collected alongside genetic data
• Statistical analyses were performed using R software
• A 100-gene panel was used for genetic analysis