NIPBL

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

One of the 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. The sister chromatids are attached to one another during the early stages of cell division by a group of proteins known as the cohesion complex. Delangin controls the interaction between the cohesion complex and the DNA that makes up the sister chromatids.

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 100 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 single protein building blocks (amino acids) in critical regions of the protein. When delangin is altered or missing, it can no longer properly regulate genes involved in development. These changes in gene regulation are likely responsible for the developmental problems characteristic of 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.