- •The South African Indian population represents a different genetic admixture compared to that of mainland India.
- •Twenty-eight different pathogenic heterozygotes were detected in 32 of the 223 patients in this study.
- •Comprehensive familial breast cancer testing is recommended for SA Indian patients as the pathogenic variants seem to be family- rather than population-specific.
- •Predictive testing of family members may relieve the financial burden on the country's healthcare system, as increased surveillance and appropriate management could prevent disease.
Knowledge of the genetic landscape of a specific population group is vital for population-specific diagnosis and treatment of familial breast cancer. Although BRCA-related diagnostic testing has long been implemented in South Africa, the genotyping approach previously failed for the SA Indian population as it was based on other SA population groups. Because this population is uniquely admixed, the lack of population-specific data resulted in the implementation of comprehensive mutation screens for BRCA1/2. A total of 223 female patients were screened for clinically actionable variants. High-resolution melting analysis (HRMA) was used to screen 88 patients for DNA alterations in the coding and splice site boundaries of BRCA1 exons 2–9, BRCA1 exons 11–23, BRCA2 exons 2–9 and BRCA2 exons 12–27. The protein truncation test (PTT) was used to screen the three larger exons (BRCA1 exon 10 and BRCA2 exons 10 and 11) for protein termination changes. Multiplex ligation-dependent probe amplification (MLPA) was used to determine the presence of larger indels and possible copy number differences. Next Generation Sequencing (NGS) was performed on the remaining 135 samples. All potential variants were confirmed by performing Sanger DNA sequencing. The search revealed 28 different pathogenic heterozygotic variants, together with nine variants of unknown significance (VUS). The results suggested that the SA Indian population represents a different genetic admixture compared to that of mainland India, as only five pathogenic variants corresponded to those reported for mainland India. Familial breast cancer testing for SA Indian patients should therefore be performed as comprehensively as possible as the pathogenic variants seem to be family- rather than population-specific. Furthermore, predictive testing of family members will contribute to relieve the financial burden on the country's healthcare system, as increased surveillance and appropriate management could prevent disease.
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Published online: June 14, 2021
Accepted: June 6, 2021
Received in revised form: February 7, 2021
Received: August 21, 2019
© 2021 Published by Elsevier Inc.