Identification of Genetic Factors in the Etiology of Autism Spectrum Disorder in Arab Families

Autism spectrum disorder (ASD) is a social interaction and communication impairment, associated with repetitive behaviors and interests. ASD has a high worldwide prevalence of about 1-1.5%. ASD is usually accompanied with heterogeneous phenotypic comorbidities, such as epilepsy and intellectual disability (ID). Twin studies suggest a high genetic contribution to ASD etiology, and several well-known rare genetic disorders are associated with ASD with high susceptibility contribution risk at about 0.5–1% of ASD cases. Moreover, several environmental factors and chromosomal abnormalities may increase the risk; the estimated known ASD-related genetic etiology is identifiable in about 25% of all ASD cases. Nevertheless, in about 75% of ASD cases the genetic etiologies remain elusive. The occurrence of ASD in the Middle East is not clear and there is a need to fill the gap in its clinical and genetic characterization in the Arab populations. In this study, nine nuclear Arab families with a child affected by ASD and epilepsy were ascertained; the known ASD causes were excluded, and were studied by Whole Exome Sequencing (WES), trio analysis and downstream filtration of identified variants. This approach identified 105 candidate genes for ASD and epilepsy across all families. We identified three potential novel candidate genes; two autosomal (SCN11A, KCNK9) and one X-linked (WNK3) harboring rare and highly possible damaging variations. Additionally, we identified variants in two genes (MPDU1 and C12orf57 ) both have been previously associated with pathogenic mutations in ASDs. We conclude that this approach is helpful in the dissection of the genetic architectures of ASD thus facilitating etiologic gene discovery and further understanding of the etiopathogenesis of ASD and related treatment and prevention methods.