Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome

Original research article by G.W. Santen et al. (2012).

Read the abstract here.

The ARID1B gene plays an important role in the early development of the brain as well as in regular cellular processes. Damaging changes have been found in children with Coffin-Siris syndrome (CSS), as well as in children with an underdeveloped corpus callosum (part of brain that connects the two hemispheres) and autism. Most often, children with CSS will have changes in both copies of their ARID1B gene. In the cases described, only one of the two copies of ARID1B was found to have a change. In this study, 2,000 children with intellectual disability were screened for genetic changes that could potentially explain their intellectual disability–and three children with deletions, or missing pieces, in one copy of the ARID1B gene were found. These deletions caused problems with gene function, and therefore likely impacted brain development.

In all three children, the deletion was not inherited from either parent (de novo). They had features like children with CSS; however, several differences were noted. All three children had some degree of intellectual disability but did not exhibit the typical hand abnormalities associated with CSS in children with changes in both copies of ARID1B.