RESUMEN
Autism spectrum disorder (ASD) manifests as a neurodevelopmental condition marked by challenges in social communication, interaction and the performing of repetitive behaviors. The prevalence of autism increases markedly on an annual basis; however, the etiology remains incompletely understood. Cytogenetically visible chromosomal abnormalities, including copy number variations (CNVs), have been shown to contribute to the pathogenesis of ASD. More than 1% of ASD conditions can be explained based on a known genetic locus, whereas CNVs account for 5-10% of cases. However, there are no studies on the Saudi Arabian population for the detection of CNVs linked to ASD, to the best of our knowledge. Therefore, the aim of the present study was to explore the prevalence of CNVs in autistic Saudi Arabian children. Genomic DNA was extracted from the peripheral blood of 14 autistic children along with four healthy control children and then array-based comparative genomic hybridization (aCGH) was used to detect CNVs. Bioinformatics analysis of the aCGH results showed the presence of recurrent and non-recurrent deletion/duplication CNVs in several regions of the genome of autistic children. The most frequent CNVs were 1q21.2, 3p26.3, 4q13.2, 6p25.3, 6q24.2, 7p21.1, 7q34, 7q11.1, 8p23.2, 13q32.3, 14q11.1-q11.2 and 15q11.1-q11.2. In the present study, CNVs in autistic Saudi Arabian children were identified to improve the understanding of the etiology of autism and facilitate its diagnosis. Additionally, the present study identified certain possible pathogenic genes in the CNV region associated with several developmental and neurogenetic diseases.
RESUMEN
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.
