Cornelia de Lange syndrome (CdLS) is a developmental disorder caused by 
mutations in NIPBL, a protein which has functionally been associated with the 
cohesin complex. Mutations in core cohesin complex components have also been 
reported in individuals with CdLS-like phenotypes. In addition to its role in 
sister chromatid cohesion, cohesin is thought to play a role in regulating gene 
expression during development. The mechanism of this gene regulation remains 
unclear, but NIPBL and cohesin have been reported to affect long-range 
chromosomal interactions, both independently and through interactions with CTCF. 
We used fluorescence in situ hybridization to investigate whether the disruption 
of NIPBL affects chromosome architecture. We show that cells from CdLS patients 
exhibit visible chromatin decompaction, that is most pronounced across gene-rich 
regions of the genome. Cells carrying mutations predicted to have a more severe 
effect on NIPBL function show more extensive chromatin decompaction than those 
carrying milder mutations. This cellular phenotype was reproduced in normal 
cells depleted for NIPBL with siRNA, but was not seen following the knockdown of 
either the cohesin component SMC3, or CTCF. We conclude that NIPBL has a 
function in modulating chromatin architecture, particularly for gene-rich areas 
of the chromosome, that is not dependent on SMC3/cohesin or CTCF, raising the 
possibility that the aetiology of disorders associated with the mutation of core 
cohesin components is distinct from that associated with the disruption of NIPBL 
itself in classical CdLS.