Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next-generation sequencing

Background Breast cancer is the most common malignancy in women worldwide. About 5%-10% are due to hereditary predisposition. The contribution of BRCA1/2 mutations to familial breast cancer in Bahrain has not been explored. The objective of this study was to investigate the spectrum of BRCA1/2 genetic variants and estimate their frequencies in familial breast cancer. We also aim to test the efficiency of the next-generation sequencing (NGS) as a powerful tool for detecting genetic variation within BRCA1/2 genes. Methods Twenty-five unrelated female patients diagnosed with familial breast cancer were screened for BRCA1/2 variants. All targeted coding exons and exon-intron boundaries of BRCA1/2 genes were amplified with 167 pairs of primers by NGS. Results We have identified two deleterious BRCA1/2 variants in two patients, one in BRCA1 gene (c.4850C>A) and other in BRCA2 gene (c.67+2T>C). In addition to the deleterious variants, we identified 24 distinct missense variants of uncertain significance, 10 of them are seen to confer minor but cumulatively significant risk of breast cancer. Conclusion Our data suggest that BRCA1/2 variants may contribute to the pathogenesis of familial breast cancer in Bahrain. It also shows that NGS is useful tool for screening BRCA1/2 genetic variants of probands and unaffected relatives.