首页|期刊导航|中华医学杂志（英文版）|Lamin C protein deficiency in the primary fibroblasts from a new laminopathy case with ovarian cystadenoma
中华医学杂志（英文版）2010，Vol.123Issue(16)：2237-2243,7.DOI:10.3760/cma.j.issn.0366-6999.2010.16.015
Lamin C protein deficiency in the primary fibroblasts from a new laminopathy case with ovarian cystadenoma
Lamin C protein deficiency in the primary fibroblasts from a new laminopathy case with ovarian cystadenoma
摘要
Abstract
Background Laminopathies are a group of rare genetic disorders characterized by multiple-tissue degeneration.We describe a new laminopathy with ovarian cystadenoma and explore its molecular etiology.Methods The case is a 15-year-old girl who presents the prominent progeroid disorders, multiple system degeneration and early-onset cystadenoma of the ovary.Candidate genes including LMNA, ZMPSTE24, PPAR G, INSR and WRN were sequenced to screen for DNA variants.The mRNA and protein expression levels of LMNA were examined in primary fibroblasts.The pathophysiological events such as morphologic alterations, cell senescence, cell proliferation,apoptosis and pRb as well as p53 protein expressions were also investigated in primary fibroblasts.Results No mutation was identified in the candidate genes screened.Nuclear abnormalities including nuclear blebs,mislocalization of lamin A/C were evident in the patient fibroblasts.Ultrastructurally, nucleus exhibited nuclear herniation and almost complete loss of peripheral heterochromatin.In addition, lamin C protein expression was markedly reduced whereas lamin A protein level was normal and no prelamin A was detected in the primary fibroblasts.Although the senescence-associated β-galactosidase staining of patient' cells was negative, cells in S phase increased in accompany with a decrease in pRb protein expression.Furthermore, increases in apoptotic cell death and p53 expression were observed.Conclusions Our data suggest that selective deficiency of lamin C protein is associated with a case of laminopathy with ovarian cystadenoma.The abnormalities in nuclear structure and alterations in gene expression such as the decrease in pRb and increase in p53 may be responsible for the multiple tissue degeneration.关键词
laminopathy/lamin C/premature aging/pRb/p53Key words
laminopathy/lamin C/premature aging/pRb/p53引用本文复制引用
CAI Meng-yin,LIANG Hua,LI Ming,BI Yan,CHEN Xiang,SUN Wei-ping,WENG Jian-ping..Lamin C protein deficiency in the primary fibroblasts from a new laminopathy case with ovarian cystadenoma [J].中华医学杂志（英文版）,2010,123(16):2237-2243,7.基金项目
This study was supported by grants from the Science and Technology Planning Project of Guangdong Province, China (No.2008B030301335), Natural Science Foundation of Guangdong Province, China (No.8151008901000196), Medical Scientific Research Foundation of Guangdong Province, China (No.B2008045), China Postdoctoral Science Foundation (No.20060390754) and Sanofi-aventis. （No.2008B030301335）
