Independent origin of 185delAG BRCA1 mutation in an Indian family

BRCA1 and BRCA2 are the two major breast cancer susceptibility genes. We tested members of a family with multiple cases of breast cancer, for mutations in the BRCA1 gene. Analysis of the PCR amplicons of all the exons (22) of the BRCA1 gene using Conformation Sensitive Gel Electrophoresis (CSGE) revealed a heteroduplex band pattern in exon 2 of the proband (III-3) in this family. The amplicon was further sequenced to assess the nature of the mutation, which revealed a deletion of AG nucleotides at the 185th position (185delAG). The two base pair deletion introduces a stop codon at the 39th amino acid residue. A similar analysis was carried out on other extended family members to evaluate their allelic status. We detected the same deletion in 7 of the 19 members tested. Two of them are males. Haplotype analysis suggested an independent origin for this mutation. Our study highlights the importance of testing hereditary cases of breast/ovarian cancer for BRCA1 mutations in extended families in order to identify high-risk individuals at a pre-clinical stage and provide genetic counseling