dc.contributor.author |
Mudau, Maria Mabyalwa
|
|
dc.contributor.author |
Seymour, Heather
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|
dc.contributor.author |
Nevondwe, Patracia
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dc.contributor.author |
Kerr, Robyn
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dc.contributor.author |
Spencer, Careni
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|
dc.contributor.author |
Feben, Candice
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dc.contributor.author |
Lombard, Zané
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dc.contributor.author |
Honey, E.M. (Engela)
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dc.contributor.author |
Krause, Amanda
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dc.contributor.author |
Carstens, Nadia
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|
dc.date.accessioned |
2024-03-14T07:45:45Z |
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dc.date.available |
2024-03-14T07:45:45Z |
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dc.date.issued |
2024-02 |
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dc.description |
DATA AVAILABILITY : The datasets used or analyzed during the current study are available on reasonable request. Variant information was submitted to ClinVar and can be viewed under Organization ID 508172. |
en_US |
dc.description.abstract |
Timely and accurate diagnosis of rare genetic disorders is critical, as it enables improved patient management and prognosis. In a resource-constrained environment such as the South African State healthcare system, the challenge is to design appropriate and cost-effective assays that will enable accurate genetic diagnostic services in patients of African ancestry across a broad disease spectrum. Next-generation sequencing (NGS) has transformed testing approaches for many Mendelian disorders, but this technology is still relatively new in our setting and requires cost-effective ways to implement. As a proof of concept, we describe a feasible diagnostic strategy for genetic disorders frequently seen in our genetics clinics (RASopathies, Cornelia de Lange syndrome, Treacher Collins syndrome, and CHARGE syndrome). The custom-designed targeted NGS gene panel enabled concurrent variant screening for these disorders. Samples were batched during sequencing and analyzed selectively based on the clinical phenotype. The strategy employed in the current study was cost-effective, with sequencing and analysis done at USD849.68 per sample and achieving an overall detection rate of 54.5%. The strategy employed is cost-effective as it allows batching of samples from patients with different diseases in a single run, an approach that can be utilized with rare and less frequently ordered molecular diagnostic tests. The subsequent selective analysis pipeline allowed for timeous reporting back of patients results. This is feasible with a reasonable yield and can be employed for the molecular diagnosis of a wide range of rare monogenic disorders in a resource-constrained environment. |
en_US |
dc.description.department |
Biochemistry |
en_US |
dc.description.department |
Genetics |
en_US |
dc.description.department |
Microbiology and Plant Pathology |
en_US |
dc.description.librarian |
hj2024 |
en_US |
dc.description.sdg |
None |
en_US |
dc.description.sponsorship |
In part by the National Research Foundation (NRF) of South Africa, the University of the Witwatersrand FRC individual grant, the National Health Laboratory Service Research Trust and South African Medical Research Council (SAMRC) with funds received from the Self-Initiated Research Grant (SIR). Open access funding provided by University of the Witwatersrand. |
en_US |
dc.description.uri |
http://link.springer.com/journal/12687 |
en_US |
dc.identifier.citation |
Mudau, M.M., Seymour, H., Nevondwe, P. et al. A feasible molecular diagnostic strategy for rare genetic disorders within resource-constrained environments.
Journal of Community Genetics 15, 39–48 (2024). https://doi.org/10.1007/s12687-023-00674-8. |
en_US |
dc.identifier.issn |
1868-310X (print) |
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dc.identifier.issn |
1868-6001 (online) |
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dc.identifier.other |
10.1007/s12687-023-00674-8 |
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dc.identifier.uri |
http://hdl.handle.net/2263/95204 |
|
dc.language.iso |
en |
en_US |
dc.publisher |
Springer |
en_US |
dc.rights |
© The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License. |
en_US |
dc.subject |
Next-generation sequencing (NGS) |
en_US |
dc.subject |
Custom-designed NGS targeted panel |
en_US |
dc.subject |
Genetic testing |
en_US |
dc.subject |
Rare diseases |
en_US |
dc.subject |
Resource-constrained environment |
en_US |
dc.title |
A feasible molecular diagnostic strategy for rare genetic disorders within resource-constrained environments |
en_US |
dc.type |
Article |
en_US |