AUTHOR=Al-Sarraj Yasser , Taha Rowaida Z. , Al-Dous Eman , Ahram Dina , Abbasi Somayyeh , Abuazab Eman , Shaath Hibah , Habbab Wesal , Errafii‬ Khaoula , Bejaoui Yosra , AlMotawa Maryam , Khattab Namat , Aqel Yasmin Abu , Shalaby Karim E. , Al-Ansari Amina , Kambouris Marios , Abouzohri Adel , Ghazal Iman , Tolfat Mohammed , Alshaban Fouad , El-Shanti Hatem , Albagha Omar M. E. 

TITLE=The genetic landscape of autism spectrum disorder in the Middle Eastern population

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1363849

DOI=10.3389/fgene.2024.1363849

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> Autism spectrum disorder (ASD) is characterized by aberrations in social interaction and communication associated with repetitive behaviors and interests, with strong clinical heterogeneity. Genetic factors play an important role in ASD, but about 75% of ASD cases have an undetermined genetic risk.</p><p><bold>Methods:</bold> We extensively investigated an ASD cohort made of 102 families from the Middle Eastern population of Qatar. First, we investigated the copy number variations (CNV) contribution using genome-wide SNP arrays. Next, we employed Next Generation Sequencing (NGS) to identify <italic>de novo</italic> or inherited variants contributing to the ASD etiology and its associated comorbid conditions in families with complete trios (affected child and the parents).</p><p><bold>Results:</bold> Our analysis revealed 16 CNV regions located in genomic regions implicated in ASD. The analysis of the 88 ASD cases identified 41 genes in 39 ASD subjects with de novo (n = 24) or inherited variants (n = 22). We identified three novel <italic>de novo</italic> variants in new candidate genes for ASD (<italic>DTX4</italic>, <italic>ARMC6</italic>, and <italic>B3GNT3</italic>). Also, we have identified 15 <italic>de novo</italic> variants in genes that were previously implicated in ASD or related neurodevelopmental disorders (<italic>PHF21A</italic>, <italic>WASF1</italic>, <italic>TCF20</italic>, <italic>DEAF1</italic>, <italic>MED13</italic>, <italic>CREBBP</italic>, <italic>KDM6B,</italic><italic>SMURF1</italic>, <italic>ADNP</italic>, <italic>CACNA1G</italic>, <italic>MYT1L</italic>, <italic>KIF13B</italic>, <italic>GRIA2</italic>, <italic>CHM</italic>, and <italic>KCNK9</italic>). Additionally, we defined eight novel recessive variants (<italic>RYR2</italic>, <italic>DNAH3</italic>, <italic>TSPYL2</italic>, <italic>UPF3B KDM5C</italic>, <italic>LYST</italic>, and <italic>WNK3</italic>), four of which were X-linked.</p><p><bold>Conclusion:</bold> Despite the ASD multifactorial etiology that hinders ASD genetic risk discovery, the number of identified novel or known putative ASD genetic variants was appreciable. Nevertheless, this study represents the first comprehensive characterization of ASD genetic risk in Qatar's Middle Eastern population.</p>