DUGi

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

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@2072@@285751

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

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