Obliteration of cardiomyocyte nuclear architecture in a patient with LMNA gene mutation.
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.
Fidziańska
Anna
A
Neuromuscular Unit, Medical Research Center, Pol. Ac. Sci., Warsaw, Poland. neurmyol@cmdik.pan.pl
Bilińska
Zofia T
ZT
Tesson
Frédérique
F
Wagner
Teresa
T
Walski
Michał
M
Grzybowski
Jacek
J
Ruzyłło
Witold
W
Hausmanowa-Petrusewicz
Irena
I
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
C494847:LMNA protein, human; D034904:Lamin Type A; D001224:Aspartic Acid; D005998:Glycine