Molecular diagnostic yield of whole-exome sequencing in Saudi autistic children with epilepsy

Abstract

Objectives: Autism spectrum disorder (ASD) is a neurological condition that affects social communication and causes repetitive behavior. Autistic children often have comorbidities such as epilepsy. Although the co-occurrence of epilepsy and ASD is frequent, the genetic basis for this association is not fully understood. Many cases of ASD and epilepsy remain unresolved without a molecular diagnosis. The purpose of this study was to determine the molecular diagnostic yield in two Saudi families with a single affected offspring with both ASD and epilepsy using whole-exome sequencing (WES).


Methods: Pediatric patients were diagnosed by a pediatric psychiatrist and neurologist, and diagnosed according to the diagnostic and statistical manual of mental disorders (DSM-V) criteria. WES was used to analyze the coding region of DNA from the two trios. Enrichment analysis was performed on the final list of genes.


Results: De novo variations were detected in eleven genes (two in ZBTB17 and FRG, and one each in CAD, CTNNA3, GILGA8J, CCZ1, CASKIN1, growth differentiation factor (GDF7), NBPF10, DUX4L4, and ZNF681). Variations in CTNNA3, GOLGA8J, CASKIN1, CCZ1, and NBPF10 genes were correlated to autism. In addition, similar studies found that CAD, CASKIN1, and GOLGA8J were candidate genes for epilepsy. FRG1 and DUX4 variations were associated with facioscapulohumeral muscular dystrophy. The expression of ZBTB17 and GDF was high in nervous system, and
variations in these genes might be correlated to autism and epilepsy.


Conclusion: Not all the genes presumed to cause ASD and epilepsy in this study were previously identified, suggesting that more genes were suspected of being involved in ASD and epilepsy co-occurrence.

Keywords:

Autistic spectrum disorder epilepsy whole-exome sequencing De novo variations Saudi families
Alharbi, A., Al-Zahrani, M., Ebbi, M., Alqurashi, M., Baqays, A., Shami, A., Alghamdi, R. A., & Alzahrani, A. (2024). Molecular diagnostic yield of whole-exome sequencing in Saudi autistic children with epilepsy. International Journal of Health Sciences, 18(3), 15–22. Retrieved from https://pub.qu.edu.sa/index.php/journal/article/view/8496
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Author Biographies

Asmaa Ali Alharbi, King Abdulaziz University

Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Maryam Hassan Al-Zahrani, King Abdulaziz University

Biochemistry Department, Faculty of Science, King Abdulaziz University

Maram Mohammed Ebbi, Ministry of Health

Consultant Psychiatrist Department of Psychiatry, Alamal Complex Developmental and Behavioral Disorders Center

May Majed Alqurashi, King Abdulaziz University

Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia

Afnan Abdulrahman Baqays, King Abdulaziz University

Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia

Ashjan Shami, King Abdulaziz University

Department of Clinical Laboratory Sciences, Taif University, Taif, Saudi Arabia.

Rana Abdullah Alghamdi, King Abdulaziz University

Department of Chemistry, College of Sciences and Arts, King Abdulaziz University, Rabigh, Saudi Arabia.

Alaa Hassan Alzahrani, King Abdulaziz University

Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

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