Mutation analysis of BUB1B gene in seven patients with PCS 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.Recently, Rahman et al. reported that MVA syndrome is caused by biallelic mutations in BUB1B. In this study, we describe BUB1B mutation in seven patients with PCS syndrome.We identified monoallelic BUB1B mutations in all seven patients; a splice site mutation, a single base deletion, a missense mutation, and a nonsense mutations in one family each. No mutation was found in the second alleles in the seven families, but western blot and haprotype analysis of BubR1 indicated a modest decrease of their transcripts. These results suggest that the patients were compound heterozygotes with the null mutation and the hypomorphic mutation of the BUB1B gene, and that >50% decrease in BubR1 expression is involved in the PCS syndrome.