Dale Dorsett and Justin C. Fay
Cornelia de Lange Syndrome (CdLS) is a devastating genetic syndrome that occurs approximately once per 10,000 births and displays slow growth, physical deformities in limbs, heart and kidney, mental retardation, speech deficits and autism. It is rarely inherited, and is usually caused by sporadic dominant mutations. Cd LS displays many features commonly seen in isolation in sporadic birth defects, thus treatments developed for it may be beneficial for development disorders of unknown etiology. CdLS is caused by mutations is genes that encode proteins that mediate sister chromatid cohesion and control gene expression. Over half the cases are caused by dominant loss-of-function mutations in NIPBL, the human ortholog of the Nipped-B Drosophila gene. The reduction in NIPBL expression in CdLS is 30 percent or less, thus a modest increase in NIPBL function will likely be beneficial. There are currently no treatments that address the root causes for CdLS and improve physical growth and mental development. The inventors have discovered a rapid, cost-effective method for screening potential therapeutic compounds for the treatment of CdLS, and have also identified useful therapeutic compounds, specifically indomethacin or acemetacin.