CDKN1C expression in Beckwith-Wiedemann syndrome patients with allele imbalance

In this study, we have examined CDKN1C expression in BWS patients with allele imbalance (AI) affecting the 11p15 region. Two of two informative patients with Al, attributable to mosaic paternal isodisomy, exhibited reduced levels of CDKN1C expression in the liver and kidney, respectively, relative to expression levels in the equivalent tissues in normal controls. Although overall expression was reduced, some expression from the paternally derived CDKN1C allele was evident, consistent with incomplete paternal imprinting of the gene. One patient showed evidence of maternal allele silencing in addition to Al. These findings show for the first time that CDKN1C expression is reduced in BWS patients with AI and suggest that CDKN1C haploinsufficiency contributes to the BWS phenotype in patients with mosaic paternal isodisomies of chromosome 11.