Considerable evidence suggests loss-of-function mutations in the chromatin remodeler CHD2 contribute to a broad spectrum of human neurodevelopmental disorders.
We also consider how CHD2 depletion can affect each of these biological mechanisms and how these defects may underpin neurodevelopmental disorders including epilepsy.
Mutations in the chromodomain helicase DNA-binding 2 (CHD2) gene have been found in patients with a range of neurodevelopmental disorders.In this issue of Neuron, Kim et al.
PMMs were identified in previously implicated high-confidence neurodevelopmental disorder risk genes, such as CHD2, CTNNB1, SCN2A, and SYNGAP1, as well as candidate risk genes with predicted functions in chromatin remodeling or neurodevelopment, including ACTL6B, BAZ2B, COL5A3, SSRP1, and UNC79.
Three sub-groups of patients were highlighted: (i) severe, symptomatic chronic neutropenia, detected early in life, and related to a known mutation in the CN spectrum (ELANE); (ii) mild to moderate benign intermittent neutropenia, detected later, and associated with mutations in genes implicated in neurodevelopmental disorders (CHD2, HUWE1); and (iii) moderate to severe intermittent neutropenia as a probably undiagnosed feature of a newly reported syndrome (KAT6A).