Multiple Recurrent Copy Number Variations (CNVs) in Chromosome 22 Including 22q11.2 Associated with Autism Spectrum Disorder

INTRODUCTION: Autism spectrum disorder (ASD) is a developmental disorder that can cause substantial social, communication, and behavioral challenges. Genetic factors play a significant role in ASD, where the risk of ASD has been increased for unclear reasons. Twin studies have shown important evidence of both genetic and environmental contributions in ASD, where the level of contribution of these factors has not been proven yet. It has been suggested that copy number variation (CNV) duplication and the deletion of many genes in chromosome 22 (Ch22) may have a strong association with ASD. This study screened the CNVs in Ch22 in autistic Saudi children and assessed the candidate gene in the CNVs region of Ch22 that is most associated with ASD. METHODS: This study included 15 autistic Saudi children as well as 4 healthy children as controls; DNA was extracted from samples and analyzed using array comparative genomic hybridization (aCGH) and DNA sequencing. RESULTS: The aCGH detected (in only 6 autistic samples) deletion and duplication in many regions of Ch22, including some critical genes. Moreover, DNA sequencing determined a genetic mutation in the TBX1 gene sequence in autistic samples. This study, carried out using aCGH, found that six autistic patients had CNVs in Ch22, and DNA sequencing revealed mutations in the TBX1 gene in autistic samples but none in the control. CONCLUSION: CNV deletion and the duplication of the TBX1 gene could be related to ASD; therefore, this gene needs more analysis in terms of expression levels.