Analysis of cells from the patients with PCS (premature chromatid separation) syndrome

Abstract

PCS syndrome is the human mitotic-spindle checkpoint disorder, characterized by mosaic variegated aneuploidy (MVA) and premature chromatid separation (PCS). The clinical manifestations include severe microcephaly, Dandy-Walker anomaly, and development of Wilms tumor. To determine the molecular basis of the disorder, we established immortalized skin fibroblast cell lines from Japanese patients. We found that the expression level of BubR1 protein was remarkably decreased in PCS cells, and only faint BubR1 signals were detected on kinetochores by immunofluorescence analysis. In PCS cells, p55cdc also failed to associate with the kinetochores. These abnormal features were normalized after introduction of BubR1 cDNA. Sequence analysis of the patients' cells detected no mutations in the BubR1 gene. These results indicated that the reduced expression of BubR1 protein might result in abolished kinetochore localization of p55cdc, and cause the mitotic checkpoint defects in PCS cells.