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J Transl Med. 2014 Jul 9;12:192. doi: 10.1186/1479-5876-12-192.

The BAG3 gene variants in Polish patients with dilated cardiomyopathy: four novel mutations and a genotype-phenotype correlation.

Author information

1
Department of Medical Genetics, Centre of Biostructure, Medical University of Warsaw, Warsaw, Pawinskiego 3C 02-106, Poland. rploski@wp.pl.

Abstract

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.

PMID:
25008357
PMCID:
PMC4105391
DOI:
10.1186/1479-5876-12-192
[Indexed for MEDLINE]
Free PMC Article

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