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Published on: August 8, 2022
Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy
Julia Daher Carneiro Marsiglia1, Flávia Laghi Credidio, Théo Gremen Mimary de Oliveira
1Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo, São Paulo, Brazil.
Insights
Genetic mutations in hypertrophic cardiomyopathy (HC) patients were identified in 48.8% of Brazilians studied. Mutations in the MYH7 gene were linked to a worse prognosis compared to MYBPC3 gene mutations.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Genetic Epidemiology
Background:
- Hypertrophic cardiomyopathy (HC) is a prevalent genetic heart disease.
- It stems from mutations in genes affecting sarcomeres, Z-disks, or calcium handling.
- HC is defined by unexplained left ventricular hypertrophy.
Purpose of the Study:
- To determine the genetic profile of Brazilian patients with HC.
- To correlate identified genotypes with clinical phenotypes.
- To investigate the molecular epidemiology of HC in Brazil.
Main Methods:
- DNA was extracted from 268 index patients in Brazil.
- Coding sequences of MYH7, MYBPC3, and TNNT2 genes were amplified and sequenced.
- Genetic mutations were identified using automatic sequencing.
Main Results:
- Causal mutations were found in 48.8% of patients.
- MYH7 (59.5%) and MYBPC3 (38.2%) harbored most mutations; 24 novel mutations were identified.
- Mutated patients were younger, had higher heart rates, and more ventricular tachycardia; MYH7 mutations correlated with larger left atria and more atrial fibrillation.
Conclusions:
- Genetic mutations in HC patients indicate a worse prognosis.
- MYH7 gene mutations are associated with a poorer outcome than MYBPC3 mutations.
- This study provides the first molecular epidemiology characterization of the three main HC genes in Brazil.
Background:
Hypertrophic cardiomyopathy (HC) is the most prevalent genetic cardiac disease caused by a mutation in sarcomeres, Z-disks, or calcium-handling genes and is characterized by unexplained left ventricular hypertrophy. The aim of this study was to determine the genetic profile of Brazilian patients with HC and correlate the genotype with the phenotype.
Methods:
We included 268 index patients from São Paulo city and 3 other cities in Brazil and extracted their DNA from whole blood. We amplified the coding sequencing of MYH7, MYBPC3, and TNNT2 genes and sequenced them with an automatic sequencer.
Results:
We identified causal mutations in 131 patients (48.8%). Seventy-eight (59.5%) were in the MYH7 gene, 50 (38.2%) in the MYBPC3 gene, and 3 (2.3%) in the TNNT2 gene. We identified 69 mutations, 24 not previously described. Patients with an identified mutation were younger at diagnosis and at current age, had a higher mean heart rate and higher nonsustained ventricular tachycardia frequency compared with those without a mutation. Patients with MYH7 gene mutations had a larger left atrium and higher frequency of atrial fibrillation than did patients with MYBPC3 gene mutations.
Conclusion:
The presence of a mutation in one of the genes suggests a worse prognosis. Mutations in the MYH7 gene, rather than in the MYBPC3 gene, were also related to a worse prognosis. This is the first work characterizing HC molecular epidemiology in the Brazilian population for the 3 most important genes.
