A molecular approach to precision medicine in South African children with Epilepsy: towards a genetics-based diagnostic service for Epilepsy
type: CreativeWork
description: Background: Epilepsy is a neurological disorder characterised by unprovoked, recurring seizures. SubSaharan Africa carries the highest burden of epilepsy in the world, owing mainly to the increased risk factors such as infectious and parasitic disease, and traumatic brain injury. A proportion of this burden is genetic, however, genetic testing for epilepsy in South Africa is limited, currently only accessible in the private healthcare sector via international referral. Genetic testing in epilepsy is an internationally recognised diagnostic tool which can inform the diagnosis and patient management, with options for precision treatment, frequently resulting in improved outcomes. The main aim of this research project, therefore, was to design and validate a next-generation sequencing (NGS) gene panel for South African paediatric patients with drug-resistant epilepsy. The panel design was aimed primarily at the developmental and epileptic encephalopathies, where the yield of informative findings is highest, and the results often carry implications for treatment. The secondary aim of the project was to perform preliminary pharmacogenetic testing, to determine if variants previously associated with antiseizure drug metabolism in other populations are present in this study group. Materials and Methods: Forty probands with clinically complex, drug-resistant epilepsy with no identified, acquired cause were recruited from the neurology epilepsy service at the Red Cross War Memorial Children's Hospital in Cape Town. All 40 probands were tested with a panel of 78 genes selected on the basis of association with disease and clinical actionability. NGS data files were subject to variant prioritisation, followed by variant confirmation by cycle sequencing, segregation analysis, and final classification according to ACMG criteria. All 40 probands were tested with two pharmacogenomic arrays, one generalised array, the Veridose® Core Panel produced by Agena Bioscience (San Diego, USA…
abstract: Background: Epilepsy is a neurological disorder characterised by unprovoked, recurring seizures. SubSaharan Africa carries the highest burden of epilepsy in the world, owing mainly to the increased risk factors such as infectious and parasitic disease, and traumatic brain injury. A proportion of this burden is genetic, however, genetic testing for epilepsy in South Africa is limited, currently only accessible in the private healthcare sector via international referral. Genetic testing in epilepsy is an internationally recognised diagnostic tool which can inform the diagnosis and patient management, with options for precision treatment, frequently resulting in improved outcomes. The main aim of this research project, therefore, was to design and validate a next-generation sequencing (NGS) gene panel for South African paediatric patients with drug-resistant epilepsy. The panel design was aimed primarily at the developmental and epileptic encephalopathies, where the yield of informative findings is highest, and the results often carry implications for treatment. The secondary aim of the project was to perform preliminary pharmacogenetic testing, to determine if variants previously associated with antiseizure drug metabolism in other populations are present in this study group. Materials and Methods: Forty probands with clinically complex, drug-resistant epilepsy with no identified, acquired cause were recruited from the neurology epilepsy service at the Red Cross War Memorial Children's Hospital in Cape Town. All 40 probands were tested with a panel of 78 genes selected on the basis of association with disease and clinical actionability. NGS data files were subject to variant prioritisation, followed by variant confirmation by cycle sequencing, segregation analysis, and final classification according to ACMG criteria. All 40 probands were tested with two pharmacogenomic arrays, one generalised array, the Veridose® Core Panel produced by Agena Bioscience (San Diego, USA…
author: McIntosh, Caitlin
keywords: Medicine
date published: 2024
date modified: 2026-07-22T22:22:44Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Clinical Laboratory Sciences

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property ID: Handle
value: http://hdl.handle.net/11427/40302