SMC3

Cornelia de Lange syndrome

At least 15 variants (also called mutations) in the SMC3 gene have been found to cause Cornelia de Lange syndrome, a developmental disorder that affects many parts of the body. Researchers estimate that variants in this gene account for 1 to 2 percent of all cases of this condition.

Most of the SMC3 gene variants that cause Cornelia de Lange syndrome either change single protein building blocks (amino acids) in the SMC3 protein or add or delete a small number of amino acids in the protein. Each of these variants alters the structure and function of the protein, which likely interferes with 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 in the SMC3 gene tend to cause a form of Cornelia de Lange syndrome with relatively mild features. Compared to variants in the NIPBL gene, which are the most common known cause of the disorder, SMC3 gene variants often cause less significant delays in development and growth and are less likely to cause major birth defects.