Fidziańska Anna, Bilińska Zofia T, Tesson Frédérique, Wagner Teresa, Walski Michał, Grzybowski Jacek, Ruzyłło Witold, Hausmanowa-Petrusewicz Irena
Neuromuscular Unit, Medical Research Center, Pol. Ac. Sci., Warsaw, Poland.
J Neurol Sci. 2008 Aug 15;271(1-2):91-6. doi: 10.1016/j.jns.2008.03.017. Epub 2008 May 27.
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.
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.
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.
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.
我们研究的目的是对一名终末期扩张型心肌病（DCM）患者的心肌细胞核结构进行免疫组织化学和超微结构分析，该患者的LMNA基因外显子3存在错义点突变，预计会导致D192G替代。
我们通过使用抗核纤层蛋白A和C的抗体进行免疫染色以及电子显微镜研究了从右心室获取的心肌内膜活检样本。分析了心肌细胞超微结构，特别关注核结构。
D192G携带者30%的心肌细胞核显示染色质紊乱和核形状改变。最令人惊讶的发现是在包膜良好的细胞核的核基质内出现了肌浆细胞器。据我们所知，这种有趣的现象首次在心肌细胞中被观察到。
该研究证明，LMNA基因中的D192G突变可能导致心肌细胞核壁破坏，从而支持人类扩张型心肌病发展的机械假说，这可能是突变特异性的。
