CHD8 dysregulation in neurodevelopment: Emerging insights into autism pathophysiology

Autism is considered a multifaceted neurodevelopmental condition, marked by impairments in social interaction, communication, and repetitive behaviours. Recent genetic research has highlighted mutations in the CHD8 (Chromodomain Helicase DNA-binding Protein 8) gene as one of the most significant risk factors associated with ASD. CHD8 encodes a chromatin remodeler protein that regulates gene expression by altering chromatin accessibility. This review aims to comprehensively review current findings on CHD8 mutations, with a focus on the gene's role in brain development, synaptic function, and ASD-related phenotypes. Previous studies have reported that CHD8 haploinsufficiency leads to altered transcriptional regulation of key neurodevelopmental genes, disrupted synaptic plasticity, and ASD-like behaviours in animal models. These results align with human genetic studies that link CHD8 mutations to macrocephaly, intellectual disability, and social deficits in ASD patients. Understanding the molecular and cellular mechanisms by which CHD8 mutations contribute to ASD can provide insights into the broader genetic architecture of the disorder and pave the way for the development of targeted therapeutic strategies. This review highlights the importance of CHD8 in neurodevelopment and emphasizes the potential of precision medicine approaches for addressing ASD-associated genetic mutations.