The endopeptidase ESPL1 (aka separase) is activated via degradation of its inhibitory chaperon, securin, to cleave RAD21 in order to allow the synchronised separation of sister chromatids during the metaphase to anaphase transition.36 Overexpression of ESPL1 in mice has been shown to result in the formation of aneuploid tumours in the mammary gland, and ESPL1 is found to be significantly overexpressed in human breast tumours.37 We screened 80 other CdLS individuals using a TaqMan CNV assay but did not identify any further cases of ESPL1 duplication. This evidence concerns the gene RAD21 and Cornelia de Lange syndrome.