Hot spots copy number variations, 15q methylation, and SHANK3 single nucleotide polymorphisms study in a group of Egyptian Autistic children

Background: Autism spectrum disorder (ASD) is a common, highly heritable and heterogeneous neurodevelopmental disorder. The etiology of ASD remains to be clarified, yet, it is postulated that both genetic and environmental factors play a pivotal role in the risk of ASD development. The work aimed to investigate the rate of CNVs of the ASD hot spots at SHANK2, 16p11.2, and 15q13.3 as well as to investigate the imprinting defects involving 15q11.2-q13 region, using the MLPA assay and to investigate the association between the SHANK3 SNPs rs9616915 and rs76224556 and ASD in a group of ASD Egyptian patients. Results: De Novo CNVs were detected in 2/40 patients (5%) in SHANK2, 2/40 patients (5%) in the 16p11.2 region, and 2/40 patients (5%) in the 15q13 region. However, no CNVs were detected in the 15q11 region which represents the area for Prader-Willi/Angelman region. Moreover, all patients showed no maternal duplication at the 15q11-q13 region. Moreover, we reported a significant association between SHANK3 SNP rs9616915 and ASD, whereas the rs76224556 genotypes were not significantly associated with ASD. Conclusion: MLPA is a cost-effective and rapid assay to detect CNV imbalances in large groups of patients and should be the first-tier test for genetic screening in ASD. The resulting data fortifies the understanding of the genotype and phenotype correlation of CNVs in patients with autism. However, further studies on larger sample sizes are still needed to evaluate the association between SNPs in the SHANK3 gene and ASD.