What are the genetic changes related to Nicolaides-Baraitser syndrome ?
Nicolaides-Baraitser syndrome is caused by mutations in the SMARCA2 gene. This gene provides instructions for making one piece (subunit) of a group of similar protein complexes known as SWI/SNF complexes. These complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and proteins that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed. To provide energy for chromatin remodeling, the SMARCA2 protein uses a molecule called ATP.  The SMARCA2 gene mutations that cause Nicolaides-Baraitser syndrome result in the production of an altered protein that interferes with the normal function of the SWI/SNF complexes. These altered proteins are able to form SWI/SNF complexes, but the complexes are nonfunctional. As a result, they cannot participate in chromatin remodeling. Disturbance of this regulatory process alters the activity of many genes, which likely explains the diverse signs and symptoms of Nicolaides-Baraitser syndrome.