A comprehensive reference for BRCA1/2 genes pathogenic variants in Iran: published, unpublished and novel

BRCA1 and BRCA2 are two prominent genes that account for about 20-40% of inherited breast cancer. Mutations in these genes are often associated with clustering of especially early-onset cancers in the family. The spectrum of BRCA variants showed a significant difference between geographic regions and ethnicities. The frequency and spectrum of BRCA mutations in Iran, a country in southwest Asia, have not yet been thoroughly studied. Here, for the first time, all published and not published BRCA pathogenic variants are presented. Among 1040 high risk families (1258 cases) which were detected, 116 families were found to carry pathogenic variants in either BRCA1 or BRCA2. Altogether 89 distinct types of pathogenic variants have been detected in Iran, including 41 in BRCA1 and 48 in BRCA2. 16 out of 89 mutations had not been previously reported in Iran and are presented for the first time in this article, among which 4 mutations are novel worldwide. 20% of families had one of the seven most commonly observed mutations, including c.81-1G > C, c.66_67delAG, c.4609C>T, c.1568delT, c.1961delA, in BRCA1 and: c.3751_3752insA, c.8585dupT in BRCA2. Combining the data from published articles and our study which has not been published before, a comprehensive table is created as a reference for entire BRCA pathogenic variants and their frequencies in Iran.