The current study builds on previous work by Krantz, who in 2004 co-led the study that discovered NIPBL, the first gene known to cause CdLS. Krantz partnered with his long-time collaborator, Laird S. Jackson, M.D., of Drexel University School of Medicine in Philadelphia. They discovered a second CdLS gene in 2007, and together they maintain the world's largest database of patients with CdLS.

In the current study, Krantz did a genome-wide analysis of mutant cell lines from 16 patients with severe CdLS. All the cells had mutations in the NIPBL gene, which plays a role in moving cohesin onto and off chromosomes.

The researchers used DNA microarrays, manufactured chips that measure how strongly different genes are expressed throughout a cell's full complement of DNA. The study team identified hundreds of genes that were dysregulated compared to controls, and also detected gene expression profiles that were unique to CdLS. Importantly, said Krantz, the expression levels of genes corresponded to the severity of the disease. The team replicated its findings in 101 additional samples.

"We found that gene expression is exquisitely regulated by cohesin and the NIBPL gene," said Krantz. "The gene expression patterns we found have great potential to be used in a diagnostic tool for Cornelia de Lange syndrome." He added that a gene array might also be developed as a single-platform tool to diagnose, from a patient's blood sample, not only CdLS, but also a variety of other developmental disorders.

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