Journal
JOURNAL OF TRANSLATIONAL MEDICINE
Volume 12, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1479-5876-12-192
Keywords
BAG3; Mutation; Penetrance; Dilated cardiomyopathy; Inherited heart disease
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Funding
- Polish National Science Centre (NCN) [2011/01/B/NZ4/03455]
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Background: BAG3 gene mutations have been recently implicated as a novel cause of dilated cardiomyopathy (DCM). Our aim was to evaluate the prevalence of BAG3 mutations in Polish patients with DCM and to search for genotype-phenotype correlations. Methods: We studied 90 unrelated probands by direct sequencing of BAG3 exons and splice sites. Large deletions/insertions were screened for by quantitative real time polymerase chain reaction (qPCR). Results: We found 5 different mutations in 6 probands and a total of 21 mutations among their relatives: the known p.Glu455Lys mutation (2 families), 4 novel mutations: p.Gln353ArgfsX10 (c.1055delC), p. Gly379AlafsX45 (c.1135delG), p.Tyr451X (c.1353C>A) and a large deletion of 17,990 bp removing BAG3 exons 3-4. Analysis of mutation positive relatives of the probands from this study pooled with those previously reported showed higher DCM prevalence among those with missense vs. truncating mutations (OR = 8.33, P = 0.0058) as well as a difference in age at disease onset between the former and the latter in Kaplan-Meier survival analysis (P = 0.006). Clinical data from our study suggested that in BAG3 mutation carriers acute onset DCM with hemodynamic compromise may be triggered by infection. Conclusions: BAG3 point mutations and large deletions are relatively frequent cause of DCM. Delayed DCM onset associated with truncating vs. non-truncating mutations may be important for genetic counseling.
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