The CHD8 gene encodes an ATP-dependent helicase enzyme that regulates gene transcription. It carries out its function by remodeling chromatin structure and recruiting histone H1 to target genes. The enzyme thus plays a role in the negative regulation of the Wnt signaling pathway and the fibroblast apoptotic process, and is an important factor in embryonic development, especially the development of the brain and digestive tract.
Mutations in the gene have been associated with susceptibility to Autism 18 (AUTS18), a subset of the Autism Spectrum disorder, wherein affected individuals exhibit macrocephaly, intellectual disability and gastrointestinal manifestations.
The CHD8 gene is located on the long arm of chromosome 14. It spans a length of 70.9 kb of DNA and its coding sequence is spread across 39 exons. The protein product encoded by this gene has a molecular mass of 290.5 kDa and consists of 2581 amino acids. An additional 262 kDa isoform of the CHD8 protein exists due to alternative splicing. The gene is ubiquitously expressed in the human body. More than 30 CHD8 gene mutations have been associated with autism spectrum disorder, including indels, splice site variants and nonsense mutations.
Monies et al. (2017) reported the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 6-year-old male from a consanguineous family, presented with fine/gross motor delay, speech delay, learning disability, developmental regression and autistic features. Using whole exome sequencing, a heterozygous mutation (4984C>T, p.R1662X) was identified in exon 26 of the patient’s CHD8 gene. As the gene had previously been tentatively linked to Autism, this finding helped confirm its association with the disorder.
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