Title : Role of genetic assessment in early-onset epilepsy management
Abstract:
Background: One of the most challenging aspects of epilepsy management is increasing the response rate to its treatment. Epilepsy is one of the disorders that is highly influenced by genetics. Gene variants in early neural development cause functional and structural impairment, resulting in seizures. Gene variants determine the threshold of seizure. The type of genetic impairment is directly associated with the response to treatment. For this purpose, this study aims to investigate the existence and determine the type of genetic variants in patients with early-onset epilepsy (EOE).
Materials and Methods: DNA was extracted from peripheral blood using a standard salting-out method. Gene variants were identified using whole-exome sequencing (WES), and sequencing data were analyzed through a two-step approach.
Results: Among 20 subjects, WES identified two novel variants. The first variant, AP3B2 (NM_001278512.2: c.3190G>A; p.Val1064Ile), was located in exon 27 and exhibited homozygosity in the proband and heterozygosity in the parents. The second variant, PIGB (NM_004855.5: c.1664G>C; p.Ter555Serext*54), was located in exon 12 and demonstrated a similar inheritance pattern. Notably, the PIGB variant was associated with elevated serum alkaline phosphatase (ALP) levels.
Conclusion: This study highlights the value of WES in identifying genetic variants associated with epilepsy, particularly the novel AP3B2 and PIGB variants. These variants provide critical insights into epilepsy pathophysiology, with the PIGB variant notably linked to elevated ALP levels, suggesting a potential biomarker for further investigation. By prioritizing detailed analysis of impactful variants, this study not only advances understanding of the genetic basis of epilepsy but also highlights the clinical significance of WES in improving diagnosis and management. Identifying actionable genetic variants enables early diagnosis, personalized treatment, and better patient outcomes, offering a pathway toward more precise and effective strategies for addressing complex neurological disorders.
