Expansion of phenotypic and genotypic data in autism spectrum disorders due to variants in the CHD8 gene.

Abstract

Autism spectrum disorders are a group of the most common disorders of neuropsychiatric development, characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns. This group of conditions frequently co-occurs with intellectual disability, epilepsy, attention-deficit hyperactivity disorder, connective tissue disorders and others. Among the most common molecular-genetic causes of autism spectrum disorders are pathogenic variants in the CHD8 gene. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and brain development in embryogenesis. 6 children and 1 adult (mother of 1 of the children) and were found to have clinically significant variants in CHD8 on whole genome sequencing (3 children and 1 adult had likely pathogenic variants, 3 children- variants of unknown significance). Their phenotype consisted of autism spectrum disorders, developmental delay, ataxia, overgrowth and other signs typically observed in patients with pathogenic variants in CHD8, as well as common comorbidities of autism spectrum disorders, such as attention-deficit hyperactivity disorder and connective tissue disorders. Additionally, 4 patients had hepatomegaly and 2- hyperbilirubinemia (1 had both) - clinical features have not been previously associated with pathogenic variants in CHD8. 2 patients also presented with cardiovascular abnormalities, primarily arrythmias and, in 1 case, cardiomyopathy- also uncharacteristic of patients with pathogenic variants in CHD8. Further research is required to determine the mechanisms underlying the abovementioned clinical features, which are likely carried out through complex interactions between CHD8 and other regulatory proteins.