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Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene

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 casesthe 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 comprehensivegenetic analysis. This study clinically and genetically assessed a large Spanish familyaffected by dilated cardiomyopathy to search for novel variations.Methods and ResultsOur study included a total of 100 family members. Clinical assessment was performed inalive, and genetic analysis was also performed in alive and 1 deceased relative. Geneticscreening included resequencing of 55 genes associated with sudden cardiac death, andSanger sequencing of main disease-associated genes. Genetic analysis identified a frameshiftvariation in BAG3 (p.H243Tfr*64) in 32 patients. Genotype-phenotype correlation identifiedsubstantial heterogeneity in disease expression. Of 32 genetic carriers (onedeceased), 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen ofthe symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographicassessment.ConclusionsWe report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familialdilated 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 ofpreventive measures

Public Library of Science (PLoS)

Author: Toro, Rocio
PĆ©rez Serra, Alexandra
Campuzano Larrea, Oscar
Moncayo Arlandi, Javier
Allegue, Catarina
Iglesias, Anna
Mangas, Alipio
Brugada, Ramon
Abstract: 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 casesthe 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 comprehensivegenetic analysis. This study clinically and genetically assessed a large Spanish familyaffected by dilated cardiomyopathy to search for novel variations.Methods and ResultsOur study included a total of 100 family members. Clinical assessment was performed inalive, and genetic analysis was also performed in alive and 1 deceased relative. Geneticscreening included resequencing of 55 genes associated with sudden cardiac death, andSanger sequencing of main disease-associated genes. Genetic analysis identified a frameshiftvariation in BAG3 (p.H243Tfr*64) in 32 patients. Genotype-phenotype correlation identifiedsubstantial heterogeneity in disease expression. Of 32 genetic carriers (onedeceased), 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen ofthe symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographicassessment.ConclusionsWe report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familialdilated 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 ofpreventive measures
Document access: http://hdl.handle.net/2072/285751
Language: eng
Publisher: Public Library of Science (PLoS)
Rights: Attribution 4.0 Spain
Rights URI: http://creativecommons.org/licenses/by/4.0/es/
Subject: Miocardi -- Malalties
Myocardium -- Diseases
Title: Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene
Type: info:eu-repo/semantics/article
Repository: Recercat

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