Clinical analysis of five CHD2 gene mutations in Chinese children with epilepsy.

• Novel mutations (c.3543T > A, c.1850A > G, c.2536C > T) have never been reported. • c.4233_4236del may be a hotspot mutation. • CHD2 patients had varying degrees of developmental delay and intellectual disability. • A significant clustering of the mutations was found near the C-terminus of the CHD2 protein. Increasing evidence reveals critical roles for CHD2 in children with developmental and epileptic encephalopathy. The aim was to present clinical analysis results of five cases with CHD2 mutations and 157 reported cases with non-copy number variations (non-CNV) of CHD2. This study recruited pediatric epilepsy patients with CHD2 mutations and clinical data from November 2016 to October 2023 in the Linyi People's Hospital, China. Whole-exome and gene panel sequencing were employed to find mutations. The HGMD and PubMed databases were examined for documented cases that had CHD2 mutations. This study reports five cases with CHD2 mutations: c.3543T > A, c.1850A > G, c.2536C > T, c.4233_4236del, c.3782G > C. Three novel mutations (c.3543T > A, c.1850A > G, c.2536C > T) have never been reported. c.4233_4236del has been reported in three cases, indicating that this locus may be a mutation hotspot. c.3782G > C has been reported in one case. All five patients had seizures before the age of four. Three patients had varying degrees of developmental delay, and four patients had varying degrees of intellectual disability. All of them had controlled seizures after Valproic acid (VPA) monotherapy or VPA in combination with other medications. Furthermore, we reviewed 157 reported cases having non-CNV mutations of CHD2. Most mutations of these cases were de novo. Epilepsy, developmental delay, and intellectual disability were the typical clinical phenotypes. We also found a significant clustering of the mutations near the C-terminus of the CHD2 protein (P < 0.001). This study reports new CHD2 genotypes and analyzes reported CHD2 mutation cases. Given its significance in epileptic encephalopathies, research on the CHD2 gene may provide new insights into epileptogenesis. [ABSTRACT FROM AUTHOR]