Main clinical features
Research of individuals with CHD8 disruptions suggest higher prevalence of ASD, macrocephaly, and gastrointestinal issues. Additionally, sleep problems, cognitive impairment and facial dysmorphology were reported (Bernier 2014).
Molecular characteristics
The CHD8 gene is located on the long arm of the 14th chromosome and is part of the chromodomain-helicase-DNA binding protein and binds to the beta-catenin for ATP-dependent chromatin remodelling.
Research suggests that loss of CHD8 function disrupts the expression of genes regulated by CHD8. This gene regulation is involved in gene co-expression networks in the fetal and developing brain, and may regulate other ASD risk genes due to its chromatin remodelling and transcriptional regulation (Cotney 2015).
Inheritance and Prevalence
CHD8 mutations are observed as both de novo and inherited events, yet has a high prevalence of recurrent de novo mutations in ASD cohorts (Wang 2016; O’Roak 2012).