title: Obliteration of cardiomyocyte nuclear architecture in a patient with LMNA gene mutation.
abstract: OBJECTIVE
  The aim of our study was to perform an immunohistochemical and ultrastructural analysis of the nuclear architecture of cardiomyocytes from an end-stage DCM patient with a missense point mutation in the exon 3 of the LMNA gene which is predicted to result in a D192G substitution.
  
  
  METHODS
  We studied endomyocardial biopsy samples taken from the right ventricle by immunostaining using antibodies against the lamins A and C and by electron microscopy. The cardiomyocyte ultrastructure was analysed, with particular attention to the nuclear architecture.
  
  
  RESULTS
  Thirty percent of cardiomyocyte nuclei from the D192G carrier showed chromatin disorganization and a changed nuclear shape. The most surprising finding was the appearance of sarcoplasmic organelles within the nuclear matrix of well enveloped nuclei. To our knowledge, this intriguing phenomenon was observed for the first time in cardiomyocytes.
  
  
  CONCLUSIONS
  The study documents that D192G mutation in LMNA gene may lead to the disruption of the nuclear wall in cardiomyocytes, thus supporting the mechanical hypothesis of dilated cardiomyopathy development in humans, which might be mutation-specific.
authors.affiliation: Neuromuscular Unit, Medical Research Center, Pol. Ac. Sci., Warsaw, Poland. neurmyol@cmdik.pan.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Fidziańska
authors.forename: Zofia T
authors.initials: ZT
authors.lastname: Bilińska
authors.forename: Frédérique
authors.initials: F
authors.lastname: Tesson
authors.forename: Teresa
authors.initials: T
authors.lastname: Wagner
authors.forename: Michał
authors.initials: M
authors.lastname: Walski
authors.forename: Jacek
authors.initials: J
authors.lastname: Grzybowski
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyłło
authors.forename: Irena
authors.initials: I
authors.lastname: Hausmanowa-Petrusewicz
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004252:DNA Mutational Analysis / Q000379:methods; D005998:Glycine / Q000235:genetics; D006801:Humans; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D020125:Mutation, Missense; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D001224:Aspartic Acid; D005998:Glycine