CHD2-Related CNS Pathologies

Abstract

Epileptic encephalopathies (EE) are severe epilepsy syndromes characterized by multiple seizure types, developmental delay and even regression. This class of disorders are increasingly being identified as resulting from de novo genetic mutations including many identified mutations in the family of chromodomain helicase DNA binding (CHD) proteins. In particular, several de novo pathogenic mutations have been identified in the gene encoding chromodomain helicase DNA binding protein 2 (CHD2), a member of the sucrose nonfermenting (SNF-2) protein family of epigenetic regulators. These mutations in the CHD2 gene are causative of early onset epileptic encephalopathy, abnormal brain function, and intellectual disability. Our understanding of the mechanisms by which modification or loss of CHD2 cause this condition remains poorly understood. Here, we review what is known and still to be elucidated as regards the structure and function of CHD2 and how its dysregulation leads to a highly variable range of phenotypic presentations.

Keywords: CHD2; developmental epileptic encephalopathy; epigenetics.

Figure 1

Domain composition of human CHD proteins. The 9 known human chromodomain helicase DNA binding (CHD) proteins, divided into their appropriate subfamilies and drawn approximately to scale with all known or predicted domains included. All structural information was derived from Uniprot [32], InterPro [33], PFAM [34] and the National Center for Biotechnology Information (NCBI) [35] web sites. (Image created in BioRender^® [36]).