What are the genetic changes related to Coffin-Siris syndrome ?
Coffin-Siris syndrome is caused by mutations in the ARID1A, ARID1B, SMARCA4, SMARCB1, or SMARCE1 gene. Each of these genes provides instructions for making one piece (subunit) of several different SWI/SNF protein complexes. SWI/SNF complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly regions of DNA are packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is often lower than when DNA is loosely packed.  Through their ability to regulate gene activity, SWI/SNF complexes are involved in many processes, including repairing damaged DNA; copying (replicating) DNA; and controlling the growth, division, and maturation (differentiation) of cells.  Although it is unclear what effect mutations in these genes have on SWI/SNF complexes, researchers suggest that the mutations result in abnormal chromatin remodeling. Disturbance of this process alters the activity of many genes and disrupts several cellular processes, which could explain the diverse signs and symptoms of Coffin-Siris syndrome.