Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene
dc.contributor.author
dc.date.accessioned
2017-05-23T12:27:06Z
dc.date.available
2017-05-23T12:27:06Z
dc.date.issued
2016-07-08
dc.identifier.uri
dc.description.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 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 frameshift
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
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science (PLoS)
dc.relation.isformatof
Reproducció digital del document publicat a: https://doi.org/10.1371/journal.pone.0158730
dc.relation.ispartof
PLoS One, 2016, vol. 11, núm. 7, p. e0158730
dc.relation.ispartofseries
Articles publicats (D-CM)
dc.rights
Attribution 4.0 Spain
dc.rights.uri
dc.subject
dc.title
Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.embargo.terms
Cap
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
025503
dc.identifier.eissn
1932-6203