NIPBL

Cornelia de Lange syndrome

Variants (also called mutations) in the NIPBL gene have been found in people with Cornelia de Lange syndrome, a developmental disorder that affects many parts of the body. Variants in this gene are the most common known cause of Cornelia de Lange syndrome, accounting for more than half of all cases.

Many different kinds of NIPBL gene variants have been reported; most lead to the production of an abnormally short (truncated), nonfunctional version of the delangin protein from one copy of the gene in each cell. These variants reduce the overall amount of delangin produced in cells, which likely alters the activity of the cohesin complex and impairs its ability to regulate genes that are critical for normal development. Although researchers do not fully understand how these changes cause Cornelia de Lange syndrome, they suspect that altered gene regulation probably underlies many of the developmental problems characteristic of the condition. Studies suggest that variants leading to a nonfunctional version of delangin tend to cause more severe signs and symptoms than variants that result in a partially functional version of the protein.