Investigating of variations in BRCA1 gene in Iranian families with breast cancer

Background: Breast cancer is one of the most common cancers among Iranian women whose relationship with mutation status in BRCA1 is previously approved. Therefore, screening of the most mutated exons in BRCA1 in hereditary breast cancer patients provides beneficial information about the main disease-causing reason. Methods: A total of 14 Iranian hereditary breast cancer patients participated in this case series study. DNA was extracted from patients’ blood samples for PCR assay. The quality of PCR products was determined using horizontal electrophoresis. Then, sequencing and analysis of the sequencing results were performed to investigate variation status in the sequences. Results: Five variants in 4 patients were found, including 1 pathogenic variant in exon 16 (H1686Q, NM_007294.3:c.5058T>A) and 4 novel intronic variants of uncertain significance (NC_000017.11:41228314G>T, NC_000017.11:41228309C>T, NC_000017.11:41228317G>T, and NC_000017.11:41203042G>A) in BRCA1. This study was the first to report 1 rare pathogenic variant in BRCA1 (H1686Q, NM_007294.3: c.5058T>A) in an Iranian family as the main disease-causing reason. Another interesting finding was non-existence of variations in almost all globally-reported and mutated exons in BRCA1. Conclusion: Investigation of these exons in BRCA1 showed the uniqueness of mutation pattern in Iranian breast cancer patients compared to other world regions. Due to the existence of other BRCA1 exons and also other predisposing genes in breast cancer, the main cause of cancer development in other participants might have been put in those exons and genes. We concluded that the most mutated exons in BRCA1 in Iranian population may not be the same as those found in other parts of the world.