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 beta-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.