Diagnosis of Epilepsy in Egyptian Patients: Insights from Whole-Exome Sequencing. | ||
| Egyptian Journal of Chemistry | ||
| Articles in Press, Accepted Manuscript, Available Online from 23 November 2025 | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejchem.2025.407056.12103 | ||
| Authors | ||
| Ayman Kilany1; Eman E.A. Mohammed* 2; Tamer H. A. Ammar3; Nahla N. Elmalah4; Mohamed Agha5; Abd Elwaged Mohamed Asmaa6; Shora Y Mostafa6 | ||
| 1Neurology Department, Medical and clinical research institute, National Research Centre, Cairo, Egypt | ||
| 2Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre | ||
| 3Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt. | ||
| 4Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt | ||
| 5Complementary medicine Department, Medical and clinical research institute, National Research Centre, Cairo, Egypt | ||
| 6Neurology Department, Al Azhar University, Cairo, Egypt. | ||
| Abstract | ||
| Background Epilepsy is a prevalent and heterogeneous neurological disorder, defined by an enduring predisposition to generate unprovoked epileptic seizures, accompanied by significant neurobiological, cognitive, psychological, and social consequences. It represents the most frequent chronic neurological condition in childhood, affecting approximately 0.5%−1% of children globally. Given its diverse etiologies, molecular diagnosis is crucial for effective management and prognostication. Objectives This study aimed to investigate the clinical characteristics and define the underlying genetic etiology of hereditary epilepsy in three unrelated Egyptian families using Whole-Exome Sequencing (WES) as a primary diagnostic tool. Subjects and Methods Five patients with epilepsy from three unrelated Egyptian families were enrolled. WES was initially performed on one index patient from each family. Subsequent segregation analysis, utilizing PCR amplification followed by Sanger sequencing, was extended to affected relatives whenever possible. Results WES successfully identified three distinct variants across three different genes. A novel likely pathogenic homozygous nonsense variant, c.912G>A; p.(Trp304*) (NM_000218.3) in the KCNQ1 gene was identified in patients 1 and 2 (Family 1). This novel variant was confirmed to be absent from HGMD, ClinVar, and gnomAD databases. Two previously reported variants were also detected: the pathogenic heterozygous missense c.1181C>T; p.(Ala394Val) (NM_001165963.4) in the SCN1A gene in patients 3 and 4 (Family 2), and the likely pathogenic heterozygous missense c.335C>T; p.(Thr112Ile) (NM_003002.4) in the SDHD gene in patient 5 (Family 3). We note that segregation analysis could not be performed for F1and F3 due to the unavailability of parental DNA, which limits the diagnosis confidence in these families Conclusion WES proved to be an efficient diagnostic strategy for elucidating the complex, heterogeneous molecular etiology of hereditary epilepsy, particularly in cases lacking a prior genetic diagnosis. Our findings successfully established a molecular diagnosis for the included patients, identified a novel pathogenic variant, and underscored the considerable molecular diversity underlying epilepsy and associated neurological phenotypes within this specific Egyptian cohort. | ||
| Keywords | ||
| Epilepsy; Whole-Exome Sequencing; WES; neurological disorder; long QT syndrome | ||
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