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Decreased Levels of BAG3 in a Family With a Rare Variant and in Idiopathic Dilated Cardiomyopathy
Begay, Rene L. Knezevic, Tijana Myers, Valerie D. Slavov, Dobromir B. Zhu, Weizhong Gowan, Katherine Graw, Sharon L. Jones, Kenneth L.
Begay, Rene L.
Knezevic, Tijana
Myers, Valerie D.
Slavov, Dobromir B.
Zhu, Weizhong
Gowan, Katherine
Graw, Sharon L.
Jones, Kenneth L.
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Journal article
Date
2014-03-13
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Medicine
Neuroscience
Pharmacology
Neuroscience
Pharmacology
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https://doi.org/10.1002/jcp.24615
Abstract
The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole-exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10-nucleotide deletion in the BCL2-associated athanogene 3 (BAG3) gene (Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C-terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end-stage HF undergoing cardiac transplantation when compared with non-failing controls. Diminished levels of BAG3 protein may be associated with both familial and non-familial forms of dilated cardiomyopathy.
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Feldman, A.M., Begay, R.L., Knezevic, T., Myers, V.D., Slavov, D.B., Zhu, W., Gowan, K., Graw, S.L., Jones, K.L., Tilley, D.G., Coleman, R.C., Walinsky, P., Cheung, J.Y., Mestroni, L., Khalili, K. and Taylor, M.R.G. (2014), Decreased Levels of BAG3 in a Family With a Rare Variant and in Idiopathic Dilated Cardiomyopathy. J. Cell. Physiol., 229: 1697-1702. https://doi.org/10.1002/jcp.24615
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Wiley
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Journal of Cellular Physiology, Vol. 229, Iss. 11
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