Document Type : Original Article
Authors
1
Neurology Department, Medical and clinical research institute, National Research Centre, Cairo, Egypt
2
Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre
3
Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
4
Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt
5
Complementary medicine Department, Medical and clinical research institute, National Research Centre, Cairo, Egypt
6
Neurology Department, Al Azhar University, Cairo, Egypt.
10.21608/ejchem.2025.407056.12103
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
Main Subjects
)
View on SCiNiTO