Wang Hu, Wang Jizheng, Zheng Weiyue, Wang Xiaojian, Wang Shuxia, Song Lei, Zou Yubao, Yao Yan, Hui Rutai
Sino-German Laboratory for Molecular Medicine, Fuwai Cardiovascular Hospital and Cardiovascular Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 Beilishi Road, 100037 Beijing, China.
Biochem Biophys Res Commun. 2006 May 26;344(1):17-24. doi: 10.1016/j.bbrc.2006.03.149.
Dilated cardiomyopathy is a form of heart muscle disease characterized by impaired systolic function and ventricular dilation. The mutations in lamin A/C gene have been linked to dilated cardiomyopathy. We screened genetic mutations in a large Chinese family of 50 members including members with dilated cardiomyopathy and found a Glu82Lys substitution mutation in the rod domain of the lamin A/C protein in eight family members, three of them have been diagnosed as dilated cardiomyopathy, one presented with heart dilation. The pathogenic mechanism of lamin A/C gene defect is poorly understood. Glu82Lys mutated lamin A/C and wild type protein was transfected into HEK293 cells. The mutated protein was not properly localized at the inner nuclear membrane and the emerin protein, which interacts with lamin A/C, was also aberrantly distributed. The nuclear membrane structure was disrupted and heterochromatin was aggregated aberrantly in the nucleus of the HEK293 cells stably transfected with mutated lamin A/C gene as determined by transmission electron microscopy.
扩张型心肌病是一种以收缩功能受损和心室扩张为特征的心肌疾病。核纤层蛋白A/C基因的突变与扩张型心肌病有关。我们在一个包括扩张型心肌病患者在内的50名成员的中国大家庭中筛查了基因突变，在8名家庭成员中发现了核纤层蛋白A/C蛋白杆状结构域中的Glu82Lys替代突变，其中3人已被诊断为扩张型心肌病，1人出现心脏扩张。核纤层蛋白A/C基因缺陷的致病机制尚不清楚。将Glu82Lys突变的核纤层蛋白A/C和野生型蛋白转染到HEK293细胞中。突变蛋白没有正确定位于内核膜，并且与核纤层蛋白A/C相互作用的emerin蛋白也分布异常。通过透射电子显微镜观察，在稳定转染了突变核纤层蛋白A/C基因的HEK293细胞核中，核膜结构被破坏，异染色质异常聚集。
