Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
Diagnosis of copy number variants using array-based comparative genomic hybridisation in fetuses and neonates with congenital abnormalities in a South African population
Greeff, Reine Athena. 2023. Effect of biological oxidants on the functioning of MEP pathway’s [Fe-S] cluster-dependent enzymes. Unpublished masters dissertation. Stellenbosch : Stellenbosch University [online]. Available at: https://scholar.sun.ac.za/items/a958dab7-9a72-4217-81a3-e15ce18081fa
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Stellenbosch : Stellenbosch University
2023
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613994850713600 |
|---|---|
| access_status_str | Open Access |
| author | Greeff, Reine Athena |
| author2 | Urban, Michael |
| author_browse | Greeff, Reine Athena Urban, Michael |
| author_facet | Urban, Michael Greeff, Reine Athena |
| author_sort | Greeff, Reine Athena |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Greeff, Reine Athena. 2023. Effect of biological oxidants on the functioning of MEP pathway’s [Fe-S] cluster-dependent enzymes. Unpublished masters dissertation. Stellenbosch : Stellenbosch University [online]. Available at: https://scholar.sun.ac.za/items/a958dab7-9a72-4217-81a3-e15ce18081fa |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/128471 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:44:59.428Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/128471 Diagnosis of copy number variants using array-based comparative genomic hybridisation in fetuses and neonates with congenital abnormalities in a South African population Greeff, Reine Athena Urban, Michael Moosa, Shahida Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics. Comparative genomic hybridization -- South Africa Genomics -- South Africa Hybridization -- Molecular aspects -- South Africa Prenatal diagnosis -- South Africa UCTD Greeff, Reine Athena. 2023. Effect of biological oxidants on the functioning of MEP pathway’s [Fe-S] cluster-dependent enzymes. Unpublished masters dissertation. Stellenbosch : Stellenbosch University [online]. Available at: https://scholar.sun.ac.za/items/a958dab7-9a72-4217-81a3-e15ce18081fa Thesis (MSc)--Stellenbosch University, 2023. ENGLISH ABSTRACT: Chromosomal microarray (CMA) is the recommended first-tier test for cytogenomic analysis in fetuses with abnormalities on ultrasound and neonates born with congenital anomalies. Chromosomal microarray detects aneuploidy and chromosomal imbalances typically detectable by conventional chromosome analysis as well as submicroscopic copy number variation (CNV) missed by karyotyping. The application of prenatal CMA in Sub-Saharan Africa remains relatively new, with limited data on its utility in our setting. From September 2019 to May 2022, clinician requested CMA were performed on prenatal and neonatal samples from private and public healthcare sectors in South Africa. Upon clinician request, quantitative fluorescence polymerase chain reaction (QF-PCR) or conventional cytogenetics were performed before CMA. Samples were analysed using aCGH on the Agilent SureScan Scanner and Agilent Cytogenomics software at Unistel Medical Laboratories. Ninety-six participants were included; 80 prenatal and 16 neonatal patients (61 originating from the private sector and 35 from the public sector) were analysed, with a mean turnaround time of 17 working days. Indications for CMA included: single system anomalies with or without soft markers 47.9%, multiple congenital anomalies (MCA) 29.2%, single anomaly with fetal growth restriction 10.4%, isolated fetal growth abnormalities with or without soft markers 6.3%, isolated increased nuchal translucency with or without soft markers 4.2%, single anomaly and an increased nuchal translucency 2%. An abnormal result was reported in 16.7% (16/96) of participants in the total population (including VUS/likely pathogenic/pathogenic). Prenatally 10% had abnormalities detected on aCGH(10/80), 6 had pathogenic findings, 3 had likely pathogenic findings, and one had a VUS reported. In the neonatal setting, 38% (6/16) which consisted of 3 participants with pathogenic findings and 3 participants with variants of uncertain significance detected. Pathogenic and likely pathogenic findings were found in 50% of participants with a single anomaly and an increased nuchal translucency (1/2), 17.9% of participants with MCA (5/28), 10.9% with single system anomalies with or without soft markers (5/46), 10% with a single anomaly with fetal growth restriction (1/10). No pathogenic or likely pathogenic findings were detected in participants referred for apparently isolated fetal growth restriction, an apparently isolated nuchal translucency, fetal growth restriction with soft markers, increased nuchal translucency with soft markers or overgrowth with soft markers. Theoretically, using 10Mb resolution, 75% (9/12, 7 prenatal and 2 post-natal) of abnormal CMAs had CNVs unlikely to be detected with karyotyping. In conclusion, in the prenatal setting aCGH had a diagnostic yield of 8.8% when excluding variants that are presumed as detectable on karyotype. The diagnostic yield of this study was slightly higher than the 6-7% in international literature, which could be attributed to all referrals for CMA being for fetal and neonatal anomalies in our study population. Since most clinically significant CNVs would have been missed if only chromosome analysis were performed, women should be offered CMA when undergoing invasive prenatal testing. AFRIKAANSE OPSOMMING: Chromosomale mikroskikking (CMS) is die aanbevole eerstevlaktoets vir sitogenomiese analise in fetusse met abnormaliteite op ultraklank en pasgeborenes met aangebore anomalieë. CMS bespeur aneuploïdie en chromosomale wanbalanse tipies waarneembaar deur konvensionele chromosoomanalise en submikroskopiese kopiegetalvariasie gemis is deur kariotipering. Die toepassing van voorgeboortelike in Afrika Suid van die Sahara bly relatief nuut, met beperkte ata oor die bruikbaarheid daarvan in ons omgewing. Van September 2019 tot Mei 2022 het die kliniek versoek dat CMS uitgevoer moet word op prenatale en neonatale monsters by private en openbare gesondheidsorgsektore in Suid-Afrika. Op versoek van die kliniek is kwantitatiewe fluoressensie polimerase kettingreaksie of konvensionele sitogenetika voor CMS uitgevoer. Monsters is ontleed deur gebruik te maak van skikking vergelykende genomiese hibridisasie op die “Agilent Sure Scanner” en “Agilent Sitogenomics” sagteware by “Unistel Medical Laboratories”. Ses en negentig studiedeelnemers is ingesluit; 80 prenatale en 16 neonatale pasiënte (61 afkomstig van die privaatsektor en 35 van die openbare) is ontleed, met 'n gemiddelde omkeertyd van 17 werksdae. Aanduidings vir CMS het ingesluit: enkelstelsel-afwykings met of sonder sagte merkers 47.9%, veelvuldige aangebore anomalieë 29.2%, enkele anomalie met fetale groeibeperking 10.4%, geïsoleerde fetale groei-afwykings met of sonder sagte merkers 6.3%, geïsoleerde verhoogde nekdeurskynendheid met of sonder sagte merkers 4.2%, en enkele anomalie met 'n verhoogde nekdeurskynendheid 2%. CMS was abnormaal in 16.7% (16/96) van die totale populasie (insluitende variante van onsekere betekenis / waarskynlik patogenies / patogenies). Voorgeboortelik het 12.5% abnormaliteite gehad (10/80), 6 het patogeniese bevindings gehad, 3 het waarskynlik patogeniese bevindinge gehad, en een het 'n variant van onsekere betekenis gerapporteer. In die neonatale arena het 38% (6/16) bestaan uit 3 individue met patogeniese bevindinge en 3 deelnemers met variante van onsekere betekenis wat opgespoor is. Patogeniese en waarskynlike patogeniese bevindings is gevind in 50% van individue met 'n enkele anomalie en 'n verhoogde nekdeurskynendheid (1/2), 17.9% van individue met veelvuldige aangebore anomalieë (5/28), 10.9% met enkelstelsel-anomalieë met of sonder sagte merkers (5/46), 10% met 'n enkele anomalie met fetale groeibeperking (1/10). Geen waarskynlik patogenies of patogenies -bevindinge is opgespoor by individue wat verwys is vir oënskynlik geïsoleerde fetale groeibeperking, 'n oënskynlik geïsoleerde nekdeurskynendheid, fetale groeibeperking met sagte merkers, verhoogde nekdeursigtigheid met sagte merkers of oorgroei met sagte merkers.Teoreties, met behulp van 10Mb resolusie, het 75% (9/12, 7 voorgeboortelike en 2 nageboortelike) van abnormale CMS kopiegetalvariasie wat onwaarskynlik is om met kariotipering opgespoor te word. 'n Hoër abnormale prenatale CMS-opsporingskoers is gerapoteer wat bo die veronderstelde kariotipe-opsporingskoers van 8.8% in vergelyking met 6% in internasionale literatuur, wat toegeskryf kan word aan alle verwysings vir CMA vir fetale en neonatale anomalieë in ons studiepopulasie. Aangesien die meeste klinies beduidende kopiegetalvariasie gemis sou word as slegs chromosoomanalise uitgevoer is, moet vroue CMS aangebied word wanneer hulle indringende prenatale toetse ondergaan. Masters 2023-02-26T06:42:21Z 2023-08-30T13:07:13Z 2023-03 2023-02-26T06:42:21Z 2023-08-31T09:18:48Z 2023-02-26T06:42:21Z 2023-08-31T09:18:48Z 2023-03 Thesis https://scholar.sun.ac.za/handle/10019.1/128471 en Stellenbosch University application/pdf xviii, 169 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Comparative genomic hybridization -- South Africa Genomics -- South Africa Hybridization -- Molecular aspects -- South Africa Prenatal diagnosis -- South Africa UCTD Greeff, Reine Athena Diagnosis of copy number variants using array-based comparative genomic hybridisation in fetuses and neonates with congenital abnormalities in a South African population |
| title | Diagnosis of copy number variants using array-based comparative genomic hybridisation in fetuses and neonates with congenital abnormalities in a South African population |
| title_full | Diagnosis of copy number variants using array-based comparative genomic hybridisation in fetuses and neonates with congenital abnormalities in a South African population |
| title_fullStr | Diagnosis of copy number variants using array-based comparative genomic hybridisation in fetuses and neonates with congenital abnormalities in a South African population |
| title_full_unstemmed | Diagnosis of copy number variants using array-based comparative genomic hybridisation in fetuses and neonates with congenital abnormalities in a South African population |
| title_short | Diagnosis of copy number variants using array-based comparative genomic hybridisation in fetuses and neonates with congenital abnormalities in a South African population |
| title_sort | diagnosis of copy number variants using array based comparative genomic hybridisation in fetuses and neonates with congenital abnormalities in a south african population |
| topic | Comparative genomic hybridization -- South Africa Genomics -- South Africa Hybridization -- Molecular aspects -- South Africa Prenatal diagnosis -- South Africa UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/128471 |
| work_keys_str_mv | AT greeffreineathena diagnosisofcopynumbervariantsusingarraybasedcomparativegenomichybridisationinfetusesandneonateswithcongenitalabnormalitiesinasouthafricanpopulation |