title: The BAG3 gene variants in Polish patients with dilated cardiomyopathy: four novel mutations and a genotype-phenotype correlation.
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.
authors.forename: Maria
authors.initials: M
authors.lastname: Franaszczyk
authors.forename: Zofia T
authors.initials: ZT
authors.lastname: Bilinska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sobieszczańska-Małek
authors.forename: Ewa
authors.initials: E
authors.lastname: Michalak
authors.forename: Justyna
authors.initials: J
authors.lastname: Sleszycka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sioma
authors.forename: Łukasz A
authors.initials: ŁA
authors.lastname: Małek
authors.forename: Dorota
authors.initials: D
authors.lastname: Kaczmarska
authors.forename: Ewa
authors.initials: E
authors.lastname: Walczak
authors.forename: Paweł
authors.initials: P
authors.lastname: Włodarski
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Hutnik
authors.forename: Blanka
authors.initials: B
authors.lastname: Milanowska
authors.forename: Zofia
authors.initials: Z
authors.lastname: Dzielinska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Religa
authors.forename: Jacek
authors.initials: J
authors.lastname: Grzybowski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zieliński
authors.affiliation: Department of Medical Genetics, Centre of Biostructure, Medical University of Warsaw, Warsaw, Pawinskiego 3C 02-106, Poland. rploski@wp.pl.
authors.forename: Rafal
authors.initials: R
authors.lastname: Ploski
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011044:Poland; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D017931:DNA Primers