Preliminary Findings on the Use of Array Comparative Genomic Hybridization in Youth with Autism Spectrum Disorder in Qatar: A Case Series Study

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with rising prevalence. Traditional diagnostic approaches often lack biological markers, making precision in diagnosis challenging. This study explores the role of array Comparative Genomic Hybridization (aCGH) in improving diagnostic accuracy for ASD. Five clinical vignettes of children diagnosed with ASD via DSM-5 or ADOS-2 were evaluated at a child and adolescent psychiatry clinic. Genome-wide oligonucleotide aCGH analysis was conducted using the Human Genome CGH Microarray kit (OGT), containing approximately 180,000 probes with 30-37 kb spacing based on the GRCh37 build. Fragile X syndrome was excluded using the Asuragen Amplidex PCR/CE FMR1 kit. The case series included boys aged 8-11 from diverse ethnic backgrounds (Asian, African, and Qatari), all presenting with varying degrees of ASD. Genetic analyses revealed significant chromosomal changes affecting eight genes, SHOX, HNF1B, COH1, AHNAK, DOCK8, TIAM1, TBL1XR1, and ALKBH8, highlighting diverse genetic contributions to ASD. These findings encompassed both chromosomal gains and losses, as well as variants of uncertain significance (VUS). The aCGH analyses provided valuable genetic insights, refining the diagnostic process and informing personalized management strategies for ASD. This suggests that aCGH is a useful tool in identifying clinically relevant genetic variations, particularly in settings with limited resources, where other diagnostic modalities may be less accessible.