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A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Diagnostic Yield of Whole Exome Sequencing in Autism Spectrum Disorder Patients at a Tertiary Center in Saudi Arabia
Abdulaziz Alasiri1, Basmah Al-Jabri2, Musaed Abukhaled1,3
1Neuroscience Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Purpose:
Autism spectrum disorder (ASD) is a clinically and genetically heterogeneous neurodevelopmental condition. Whole‑exome sequencing (WES) is a pivotal diagnostic tool, though its yield varies across populations. This study aimed to determine the diagnostic yield and characterize the genetic spectrum identified by WES in a pediatric ASD cohort from Saudi Arabia.
Methods:
We conducted a retrospective cohort study of 288 children (< 14 years) with DSM‑5‑confirmed ASD who underwent clinical WES at a tertiary center between 2021 and 2024. Variants were classified according to ACMG/AMP guidelines.
Results:
The overall diagnostic yield for pathogenic or likely pathogenic variants was 30% (86/288). Variants of uncertain significance were identified in 22% (63/288) of patients. Recurrently affected genes included SHANK3, SCN2A, SYNGAP1, CAMK2A, GRIN2B, and CNTNAP2. Notably, variants in GFAP, a gene primarily associated with Alexander disease, were found in six patients presenting with ASD, macrocephaly, and developmental delay.
Conclusions:
WES provided a molecular diagnosis in 30% of this Saudi ASD cohort. The identification of GFAP variants raises the hypothesis that astrocytic dysfunction may play a role in a subset of ASD cases, though this finding requires independent replication and functional validation. These results underscore the clinical utility of WES and highlight the need for population‑specific genomic resources.
