title: LMNA mutations in Polish patients with dilated cardiomyopathy: prevalence, clinical characteristics, and in vitro studies.
abstract: BACKGROUND
  LMNA mutations are most frequently involved in the pathogenesis of dilated cardiomyopathy with conduction disease. The goal of this study was to identify LMNA mutations, estimate their frequency among Polish dilated cardiomyopathy patients and characterize their effect both in vivo and in vitro.
  
  
  METHODS
  Between January, 2008 and June, 2012 two patient populations were screened for the presence of LMNA mutations by direct sequencing: 66 dilated cardiomyopathy patients including 27 heart transplant recipients and 39 dilated cardiomyopathy patients with heart failure referred for heart transplantation evaluation, and 44 consecutive dilated cardiomyopathy patients, referred for a family evaluation and mutation screening.
  
  
  RESULTS
  We detected nine non-synonymous mutations including three novel mutations: p.Ser431*, p.Val256Gly and p.Gly400Argfs*11 deletion. There were 25 carriers altogether in nine families. The carriers were mostly characterized by dilated cardiomyopathy and heart failure with conduction system disease and/or complex ventricular arrhythmia, although five were asymptomatic. Among the LMNA mutation carriers, six underwent heart transplantation, fourteen ICD implantation and eight had pacemaker. In addition, we obtained ultrastructural images of cardiomyocytes from the patient carrying p.Thr510Tyrfs*42. Furthermore, because the novel p.Val256Gly mutation was found in a sporadic case, we verified its pathogenicity by expressing the mutation in a cellular model.
  
  
  CONCLUSIONS
  In conclusion, in the two referral centre populations, the screening revealed five mutations among 66 heart transplant recipients or patients referred for heart transplantation (7.6%) and four mutations among 44 consecutive dilated cardiomyopathy patients referred for familial evaluation (9.1%). Dilated cardiomyopathy patients with LMNA mutations have poor prognosis, however considerable clinical variability is present among family members.
authors.affiliation: Laboratory of Molecular Biology, Institute of Cardiology, Warsaw, Alpejska 42 04-628, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Saj
authors.forename: Zofia T
authors.initials: ZT
authors.lastname: Bilinska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Tarnowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sioma
authors.forename: Pierrette
authors.initials: P
authors.lastname: Bolongo
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Sobieszczanska-Malek
authors.forename: Ewa
authors.initials: E
authors.lastname: Michalak
authors.forename: Dorota
authors.initials: D
authors.lastname: Golen
authors.forename: Lukasz
authors.initials: L
authors.lastname: Mazurkiewicz
authors.forename: Lukasz
authors.initials: L
authors.lastname: Malek
authors.forename: Ewa
authors.initials: E
authors.lastname: Walczak
authors.forename: Anna
authors.initials: A
authors.lastname: Fidzianska
authors.forename: Jacek
authors.initials: J
authors.lastname: Grzybowski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Przybylski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zielinski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Korewicki
authors.forename: Frederique
authors.initials: F
authors.lastname: Tesson
authors.forename: Rafal
authors.initials: R
authors.lastname: Ploski
mesh_terms: D000328:Adult; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D002460:Cell Line; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000235:genetics / Q000473:pathology; D016027:Heart Transplantation / Q000379:methods; D006579:Heterozygote; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D051379:Mice; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D032446:Myoblasts / Q000378:metabolism*; D009206:Myocardium / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000473:pathology; D010375:Pedigree; D011044:Poland / Q000453:epidemiology; D015995:Prevalence; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A