Related Experiment Video
Updated: Mar 18, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene
Rocio Toro1, Alexandra Pérez-Serra2, Oscar Campuzano2,3
1Medicine Department, School of Medicine, Cadiz, Spain.
Insights
A novel BAG3 gene variation (p.H243Tfr*64) causes familial dilated cardiomyopathy, leading to severe heart conditions, especially in younger patients. Genetic screening in families aids early risk identification and preventive strategies for dilated cardiomyopathy.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Genetic Medicine
Background:
- Dilated cardiomyopathy is a leading cause of heart failure and transplantation, often inherited.
- Over 60 genes are linked to dilated cardiomyopathy, yet mutations remain unidentified in 30% of familial cases.
- A large Spanish family with familial dilated cardiomyopathy was studied to identify novel genetic variations.
Purpose of the Study:
- To clinically and genetically assess a large Spanish family affected by dilated cardiomyopathy.
- To identify novel genetic variations contributing to familial dilated cardiomyopathy.
- To understand genotype-phenotype correlations in affected family members.
Main Methods:
- Clinical assessment of 100 family members (alive and 1 deceased).
- Genetic analysis including resequencing of 55 sudden cardiac death genes and Sanger sequencing.
- Identification of genetic variations and genotype-phenotype correlation.
Main Results:
- A novel frame-shift variation in the BAG3 gene (p.H243Tfr*64) was identified in 32 family members.
- Significant heterogeneity in disease expression was observed among carriers.
- Twenty-one of 32 carriers were clinically affected, 10 were asymptomatic, and 17 showed proto-diastolic septal knock.
Conclusions:
- The BAG3 p.H243Tfr*64 variation is a novel pathogenic cause of familial dilated cardiomyopathy.
- This variation is associated with a more severe phenotype, particularly in younger individuals.
- Family-based genetic analysis allows early identification of at-risk individuals and implementation of preventive measures for dilated cardiomyopathy.
Background:
Dilated cardiomyopathy, a major cause of chronic heart failure and cardiac transplantation, is characterized by left ventricular or biventricular heart dilatation. In nearly 50% of cases the pathology is inherited, and more than 60 genes have been reported as disease-causing. However, in 30% of familial cases the mutation remains unidentified even after comprehensive genetic analysis. This study clinically and genetically assessed a large Spanish family affected by dilated cardiomyopathy to search for novel variations.
Methods And Results:
Our study included a total of 100 family members. Clinical assessment was performed in alive, and genetic analysis was also performed in alive and 1 deceased relative. Genetic screening included resequencing of 55 genes associated with sudden cardiac death, and Sanger sequencing of main disease-associated genes. Genetic analysis identified a frame-shift variation in BAG3 (p.H243Tfr*64) in 32 patients. Genotype-phenotype correlation identified substantial heterogeneity in disease expression. Of 32 genetic carriers (one deceased), 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen of the symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographic assessment.
Conclusions:
We report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familial dilated cardiomyopathy. This variation correlates with a more severe phenotype of the disease, mainly in younger individuals. Genetic analysis in families, even asymptomatic individuals, enables early identification of individuals at risk and allows implementation of preventive measures.
More Related Videos
Related Concept Videos
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:30Cardiomyopathy II: Dilated Cardiomyopathy
01:25Cardiomyopathy I: Introduction and Classification
01:31Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
01:31Translation
Translation Produces the Building Blocks of Life
Proteins are...
01:30Point and Frameshift Mutations