Caracterização Genética e Clínica de uma Coorte de Pacientes com Cardiomiopatia Hipertrófica no Sul do Brasil

Thais Beuren; Fernando Scolari; Fernanda Sperb-Ludwig; Filipe Ferrari; Arthur Rossi; Rafael Zawislak; Peter van Tintelen; Ricardo Stein

doi:10.36660/abc.20250420

Caracterização Genética e Clínica de uma Coorte de Pacientes com Cardiomiopatia Hipertrófica no Sul do Brasil

Translated title of the contribution: Genetic and Clinical Characterization of a South-Brazilian Hypertrophic Cardiomyopathy Cohort

Thais Beuren
, Fernando Scolari
, Fernanda Sperb-Ludwig
, Filipe Ferrari
, Arthur Rossi
, Rafael Zawislak
, Peter van Tintelen
, Ricardo Stein^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Translated title of the contribution	Genetic and Clinical Characterization of a South-Brazilian Hypertrophic Cardiomyopathy Cohort
Original language	Portuguese
Article number	e20250420
Journal	Arquivos Brasileiros de Cardiologia
Volume	123
Issue number	2
DOIs	https://doi.org/10.36660/abc.20250420
Publication status	Published - Feb 2026

Keywords

Hypertrophic Cardiomyopathy
Genetic Testing
High-Throughput Nucleotide Sequencing
Brazil

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0066-782x-abc-123-2-e20250420-en.x12869Final published version, 579 KBLicence: CC BY

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@article{bfa520b5766447ee841d4d46c71291fd,

title = "Caracteriza{\c c}{\~a}o Gen{\'e}tica e Cl{\'i}nica de uma Coorte de Pacientes com Cardiomiopatia Hipertr{\'o}fica no Sul do Brasil",

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.",

keywords = "Hypertrophic Cardiomyopathy, Genetic Testing, High-Throughput Nucleotide Sequencing, Brazil",

author = "Thais Beuren and Fernando Scolari and Fernanda Sperb-Ludwig and Filipe Ferrari and Arthur Rossi and Rafael Zawislak and \{van Tintelen\}, Peter and Ricardo Stein",

year = "2026",

month = feb,

doi = "10.36660/abc.20250420",

language = "Portuguese",

volume = "123",

journal = "Arquivos Brasileiros de Cardiologia",

issn = "0066-782X",

publisher = "Sociedade Brasileira de Cardiologia",

number = "2",

}

TY - JOUR

T1 - Caracterização Genética e Clínica de uma Coorte de Pacientes com Cardiomiopatia Hipertrófica no Sul do Brasil

AU - Beuren, Thais

AU - Scolari, Fernando

AU - Sperb-Ludwig, Fernanda

AU - Ferrari, Filipe

AU - Rossi, Arthur

AU - Zawislak, Rafael

AU - van Tintelen, Peter

AU - Stein, Ricardo

PY - 2026/2

Y1 - 2026/2

N2 - 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.

AB - 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.

KW - Hypertrophic Cardiomyopathy

KW - Genetic Testing

KW - High-Throughput Nucleotide Sequencing

KW - Brazil

U2 - 10.36660/abc.20250420

DO - 10.36660/abc.20250420

M3 - Article

C2 - 41880433

SN - 0066-782X

VL - 123

JO - Arquivos Brasileiros de Cardiologia

JF - Arquivos Brasileiros de Cardiologia

IS - 2

M1 - e20250420

ER -

Caracterização Genética e Clínica de uma Coorte de Pacientes com Cardiomiopatia Hipertrófica no Sul do Brasil

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Keywords

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