Mutation Glu82Lys in lamin A/C gene is associated with cardiomyopathy and conduction defect.
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.
Wang
Hu
H
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.
Wang
Jizheng
J
Zheng
Weiyue
W
Wang
Xiaojian
X
Wang
Shuxia
S
Song
Lei
L
Zou
Yubao
Y
Yao
Yan
Y
Hui
Rutai
R
D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D002478:Cells, Cultured; D002648:Child; D005260:Female; D018698:Glutamic Acid / Q000737:chemistry / Q000235:genetics; D006327:Heart Block / Q000235:genetics* / Q000378:metabolism; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D034904:Lamin Type A / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000737:chemistry / Q000648:ultrastructure; D009687:Nuclear Proteins; D010375:Pedigree; D017354:Point Mutation; D013946:Thymopoietins / Q000032:analysis / Q000378:metabolism
D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin; C440308:lamin C; D018698:Glutamic Acid; D008239:Lysine