Haematology and Cell Biology

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Browsing Haematology and Cell Biology by Author "Combrink, H. M. V. E."

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    Molecular screening of the South African Indian population for BRCA1 and BRCA2 using high resolution melting analysis
    (University of the Free State, 2016-01) Combrink, H. M. V. E.; Van der Merwe, N. C.; Visser, B.
    English: The lifetime risk for developing breast cancer within the Indian population of South Africa is one in 17. Disease causing mutations in BRCA1/2 increase the risk of developing this disease by up to 80%. The main objective of this study was to screen this unique population for mutations in BRCA1/2. This was achieved by optimising High Resolution Melting Analysis (HRMA) as the screening technique for the smaller exons while the Protein Truncation Test (PTT) was used to screen exon 11 for BRCA1/2 respectively. In order to optimise HRMA, a full BRCA1/2 screen was performed on 24 patients from four different South African ethnic groups using Single-Stranded Conformation Polymorphism/ Heteroduplex Analysis (SSCP/HA). These results were compared to a HRMA screen performed on the same patients. No differences were observed between the sensitivity of the three techniques and the turnaround time (TAT) was considerably less for HRMA. The entire cohort used in this study came from 50 unrelated South African Indian patients. A full BRCA1/2 screen was performed on these patients. A total of nine different pathogenic mutations were detected. Four of the disease causing mutations (BRCA1 c.1360_1361delAG, p.Ser454Terfs; c.3593T>A, p.Leu1198Ter and BRCA2 c.5279C>G, p.Ser1760Ter; 5563C>G, p.Ser1855Ter) were detected using PTT, whereas the other five mutations (BRCA1 185delAG, p.Leu22_Glu23LeuValfs; c.191G>A, p.Cys64Tyr; c.5365_5366delGCinsA, p.Ala1789_Ile1790LeuTrpfs and BRCA2 c.9435_9436delGT, Val3145_Phe3146=fs; c.8754+1G>A, IVS21+1G>A) were detected using HRMA. Three unrelated patients were carriers of the splice site mutation found within BRCA2 exon 21. The research that was conducted, contributed to the knowledge pool for predictive testing in the clinical setting of South Africa and gave insight into possible diagnostic tests that could be designed for this population.