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The utility of next generation sequencing at a Paediatric Neurology Department at Tygerberg Hospital, Western Cape, South Africa
Thesis (MPhil) -- Stellenbosch University, 2022.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2022
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| _version_ | 1867613743816376320 |
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| access_status_str | Open Access |
| author | Van Niekerk, Margaretha Susan |
| author2 | Van Toorn, Ronald |
| author_browse | Van Niekerk, Margaretha Susan Van Toorn, Ronald |
| author_facet | Van Toorn, Ronald Van Niekerk, Margaretha Susan |
| author_sort | Van Niekerk, Margaretha Susan |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MPhil) -- Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/126164 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:41:00.180Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/126164 The utility of next generation sequencing at a Paediatric Neurology Department at Tygerberg Hospital, Western Cape, South Africa Van Niekerk, Margaretha Susan Van Toorn, Ronald Moosa, Shahida Solomons, Regan Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health. High-throughput nucleotide sequencing Human chromosome abnormalities -- Diagnosis Comparative genomic hybridization Fluorescence in situ hybridization Cytodiagnosis -- South Africa Pediatrics -- South Africa Nervous system -- Diseases -- South Africa Children -- Disease -- South Africa Thesis (MPhil) -- Stellenbosch University, 2022. ENGLISH ABSTRACT: Introduction: Next-generation sequencing (NGS) technologies have improved diagnostics in rare genetic diseases. Neurological disorders are a group of disorders to which NGS tests have been vastly applied to. Currently, when and how to use NGS testing in a clinic setting is an unsolved issue, although new research results provide evidence favouring its use as a firstline diagnostic modality in many childhood neurological disorders in high-income countries. Objectives: To investigate the clinical utility of NGS in a tertiary paediatric neurology clinic in a resource-constrained Sub-Saharan setting. Design. We performed a retrospective, 41-month long study, in a single tertiary-level neurology clinic in South Africa, comprising consecutive paediatric neurology patients for whom an NGS-based diagnostic test was requested. Twenty-four different disease-group specific NGS-based gene panels were utilized in the study and the results categorized into the following categories: positive (pathogenic/likely pathogenic), variant of unknown significance, or negative. Result interpretation and careful matching of the variant to the clinical phenotype was performed. Subsequently, questionnaires were administered to some of the caregivers where a pathological variant was identified. Results: The overall diagnostic yield (DY) was 53% (66/124 patients). It was highest for Neuromuscular disorders (DY 64%), Cerebral palsy spectrum disorders (DY 54%) (9/16 patients), followed by Epilepsies (DY 44%)(28/63 patients). In 38%, an inconclusive molecular diagnosis was obtained. The small number of patients in some phenotypic groups limited the interpretation of specific diagnostic yields. The higher yield of the gene panel for neuromuscular disorders suggests that NGS may be a more cost-effective first-line test in well-defined phenotypes. Most caregivers (97%) expressed relief in knowing the diagnosis. Conclusion: We present daily clinical practice evidence that, even with the constraints of the South African health system, for half of the children with neurological disorders of undetermined aetiology, a definitive diagnosis can be reached with NGS. The diagnostic yield of our study is similar to previously reported paediatric cohorts. Our experience highlights the feasibility and clinical utility of NGS in the management of paediatric neurology patients. Future prospective clinical trials using NGS are required to establish efficacy and costeffectiveness, especially in resource-constrained settings. AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar. Masters 2022-11-21T17:02:25Z 2023-01-16T12:53:22Z 2022-11-21T17:02:25Z 2023-01-16T12:53:22Z 2022-09 Thesis http://hdl.handle.net/10019.1/126164 en_ZA Stellenbosch University 51 pages application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | High-throughput nucleotide sequencing Human chromosome abnormalities -- Diagnosis Comparative genomic hybridization Fluorescence in situ hybridization Cytodiagnosis -- South Africa Pediatrics -- South Africa Nervous system -- Diseases -- South Africa Children -- Disease -- South Africa Van Niekerk, Margaretha Susan The utility of next generation sequencing at a Paediatric Neurology Department at Tygerberg Hospital, Western Cape, South Africa |
| title | The utility of next generation sequencing at a Paediatric Neurology Department at Tygerberg Hospital, Western Cape, South Africa |
| title_full | The utility of next generation sequencing at a Paediatric Neurology Department at Tygerberg Hospital, Western Cape, South Africa |
| title_fullStr | The utility of next generation sequencing at a Paediatric Neurology Department at Tygerberg Hospital, Western Cape, South Africa |
| title_full_unstemmed | The utility of next generation sequencing at a Paediatric Neurology Department at Tygerberg Hospital, Western Cape, South Africa |
| title_short | The utility of next generation sequencing at a Paediatric Neurology Department at Tygerberg Hospital, Western Cape, South Africa |
| title_sort | utility of next generation sequencing at a paediatric neurology department at tygerberg hospital western cape south africa |
| topic | High-throughput nucleotide sequencing Human chromosome abnormalities -- Diagnosis Comparative genomic hybridization Fluorescence in situ hybridization Cytodiagnosis -- South Africa Pediatrics -- South Africa Nervous system -- Diseases -- South Africa Children -- Disease -- South Africa |
| url | http://hdl.handle.net/10019.1/126164 |
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