Clinical utility of next-generation sequencing in children with cryptogenic cerebral palsy; a cohort study from a tertiary paediatric neurology clinic in the Western Cape Province of South Africa

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dc.contributor.advisorVan Toorn, Ronalden_ZA
dc.contributor.advisorSolomons, Reganen_ZA
dc.contributor.authorMohammed, Hiba Hamid Ahmeden_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health. Paediatric Neurology.en_ZA
dc.date.accessioned2023-11-25T13:04:59Zen_ZA
dc.date.accessioned2024-01-08T18:45:58Zen_ZA
dc.date.available2023-11-25T13:04:59Zen_ZA
dc.date.available2024-01-08T18:45:58Zen_ZA
dc.date.issued2023-11en_ZA
dc.descriptionThesis (MPhil)--Stellenbosch University, 2023.en_ZA
dc.description.abstractENGLISH ABSTRACT: Introduction: Cerebral palsy (CP) is the most common motor disability in childhood. Both genetic and environmental factors contribute to the aetiology of CP. Recent advances in molecular genetics such as next generation sequencing (NGS) and whole exome sequencing (WES) have revolutionized the understanding of aetiology by more precisely classifying these disorders with a molecular cause. This study aimed to determine the clinical utility of NGS/WES in children with cryptogenic CP. Methods: Data was collected from 218 consecutive children with CP aged 3.6-10.5 years, referred over an 18-month period, to the tertiary paediatric neurology service at Tygerberg Academic Hospital. Results: Cryptogenic CP cases accounted for 24.3% (53/218) of cases. NGS/WES was performed in 66% (35/53). Pathogenic/likely pathogenic variants were identified in 37.2% (13/35) within the following genes: ATP1A3, SCN2A, ATM, FOXG1, UBE3A, KCNA2, ADAR1, QDPR, GCDH, SAMHD1, PLP1 duplication and SLC16A2. Cryptogenic CP cases were more likely to exhibit dyskinetic (odds ratio (OR)= 2.86; P-value=0.01; 95% CI=1.34-6.11) or hypotonic (OR =24.96; P-value=0.01; 95% CI=2.99-208.05) phenotypes, and less likely present with seizures (OR=0.23, P-value=0.01; 95% CI=0.11-0.46). Conclusion: The high rate of detecting causative genetic variants in the study, 37.2%, suggests that NGS/WES should be considered as first-line investigations in children with cryptogenic CP, especially those with dyskinetic or hypotonic subtypes and normal or non-specific MRI findings.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.af_ZA
dc.description.versionMastersen_ZA
dc.format.extentv, 46 pagesen_ZA
dc.identifier.urihttps://scholar.sun.ac.za/handle/10019.1/129000en_ZA
dc.language.isoen_ZAen_ZA
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subject.lcshCerebral palsyen_ZA
dc.subject.lcshPaediatricsen_ZA
dc.subject.lcshHigh-throughput nucleotide sequencingen_ZA
dc.subject.lcshWhole exome sequencingen_ZA
dc.subject.lcshDiseases -- Causes and theories of causationen_ZA
dc.titleClinical utility of next-generation sequencing in children with cryptogenic cerebral palsy; a cohort study from a tertiary paediatric neurology clinic in the Western Cape Province of South Africaen_ZA
dc.typeThesisen_ZA
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