Investigating the Role of the Zinc Finger Protein ZC2HC1C on Autism Spectrum Disorder Susceptibility

Background and Objectives: Zinc finger proteins are important transcription factors that regulate gene expression and play a critical role in neurodevelopment including autism spectrum disorders (ASDs). They are involved in a variety of cellular processes, including cell proliferation, differentiation, and apoptosis. Materials and Methods: Whole-exome sequencing (WES) analysis on a patient diagnosed with ASD. Results: Sequencing identified a homozygous insertion causing a stop codon, resulting in the removal of several functional domains including the zinc finger C2HC/C3H type of the ZC2HC1C protein. To date, no MIM entry has been assigned to the detected gene. In silico predictions described the variant as likely pathogenic, indicating an autosomal recessive inheritance pattern. In this study, we hypothesize that this homozygous mutation disrupts protein function and may represent a susceptibility gene for autism. The parents and the patient’s sister were healthy and carry the variant in the heterozygous condition. This gene is expressed in brain tissues showing high expression in both the choroid plexus (ChP) and midbrain, whose dysfunctions, as reported, may lead to ASD. Moreover, predictive pathway analyses indicated the probable involvement of this gene in primary cilia development. This process has been frequently linked to neurodevelopmental impairments, such as autism, as documented in previous studies. Conclusions: Further analyses are needed via in vitro functional assays or by ZC2HC1C gene knockout to validate its functional role.