NIPBL

The NIPBL gene provides instructions for making a protein called delangin. Although the exact function of this protein is unknown, it plays an important role in human development. Before birth, delangin is present in developing limbs, the bones of the skull and face, the spinal column, the heart, and other parts of the body.

One of the likely functions of delangin is to help control the activity of chromosomes during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached together during the early stages of cell division. Delangin appears to control the group of proteins (called the cohesion complex) that holds the sister chromatids together until the cell splits into two.

Additionally, delangin regulates the activity of certain genes that are critical for normal development, particularly genes that coordinate the development of tissues that will become the limbs and face. Studies suggest that delangin is also involved in the repair of damaged DNA.

Cornelia de Lange syndrome - caused by mutations in the NIPBL gene

More than 60 mutations in the NIPBL gene have been identified in people with Cornelia de Lange syndrome. Most of these mutations lead to the production of an abnormally small, nonfunctional version of the delangin protein. Other mutations impair the function of delangin by changing a single protein building block (amino acid) in critical regions of the protein. When delangin is altered or missing, it can no longer properly regulate genes involved in normal development. These changes in gene regulation are likely responsible for the developmental problems found in Cornelia de Lange syndrome. Studies suggest that mutations leading to a nonfunctional version of delangin tend to cause more severe signs and symptoms than mutations that change a single amino acid in the protein.