Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene.
PLoS One
; 11(7): e0158730, 2016.
Article
em En
| MEDLINE
| ID: mdl-27391596
ABSTRACT
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 ANDRESULTS:
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.
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Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
/
Mutação da Fase de Leitura
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Reguladoras de Apoptose
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article