Next- Generation Sequencing to Identify Disease Causing Variants in Individuals with Epilepsy (2024)

Undergraduate: Rayaan Bashir

Faculty Advisor: Erin Heinzen
Department: Eshelman School of Pharmacy, Neuroscience

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Objective: The objective of this study was to utilize Next-Generation Sequencing (NGS) to identify disease-causing variants in individuals with epilepsy, with a focus on a case study of a 7-year-old male diagnosed with Idiopathic West syndrome exhibiting a range of symptoms.

Methods: Our research utilized a multifaceted approach combining NGS and Sanger Sequencing. Initially, NGS identified a potential ASH1L gene variant in the patient which led to the design of primers for PCR amplification of the targeted gene region and subsequent validation through gel electrophoresis. The optimized PCR conditions facilitated replication using blood samples from the patient and parents, with the purified samples analyzed via Sanger Sequencing to determine the specific nature of the ASH1L mutation.

Results: The analysis revealed a mutation absent in the maternal genetic profile but present in the paternal and patient's genomes, suggesting a paternal inheritance pattern. This mutation, a change from a typical G genotype to an A genotype at the region of interest, underscores the genetic underpinnings of epilepsy, potentially contributing to the development of the condition in the patient.

Conclusion: This study highlights the power of integrating NGS with traditional sequencing methods to uncover genetic variants responsible for epilepsy. Our findings emphasize the significance of genetic factors in the disease's etiology and pave the way for further research into the genetic complexities of neurological disorders. The identification of the ASH1L mutation in this case study provides insights into the hereditary nature of epilepsy and underscores the importance of genetic analysis of neurological conditions.