Abstract Information


Presenting Author(s) Emma Tonkin
Abstract Title NIPBL, encoding a homologue of fungal Scc2-type sister chromatid cohesion proteins and Drosophila Nipped-B, is mutated in Cornelia de Lange syndrome
Full author List Emma T. Tonkin, Tzu-Jou Wang, Steven Lisgo, Michael J. Bamshad and Tom Strachan
Text of abstract Cornelia de Lange syndrome (CdLS) is a multiple malformation disorder characterised by dysmorphic facial features, mental retardation, growth delay, and limb reduction defects. We have identified and characterised a novel gene, NIPBL, that is mutated in CdLS patients, and established its structure and that of rodent and zebrafish homologues, naming its protein product delangin. Vertebrate delangins exhibit significant homology to orthologues in flies, worms, plants and fungi, including Scc2-type sister chromatid cohesion proteins, and also Drosophila Nipped-B, which is known to regulate Ultrabithorax and cut. The pattern of embryonic NIPBL expression is generally consistent with CdLS pathogenesis. Considering known Nipped-B interactions, we propose that perturbed delangin function causes inappropriate activation of DLX genes, thereby contributing to the proximo-distal limb patterning defects in CdLS. Very recently, Nipped-B has been shown to have a role in sister chromatid cohesion as well as in developmental gene regulation and we propose that vertebrate delangins also have a similar dual role that suggests possible parallels with Roberts syndrome. The general role in sister chromatid cohesion could be satisfied by a basal level of expression but the role in target gene developmental regulation could be expected to require high expression in tissues where the target genes are active.
Which session is your work most relevant to: Human limb abnormalities