Deletion of exons 1a-2 of BRCA1: a rather frequent pathogenic abnormality

Women carrying a pathogenic mutation in either BRCA1 or BRCA2 have a major risk of developing breast and/or ovarian cancer. The majority of mutations in these genes are small point mutations. Since the development of multiplex ligation-dependent probe amplification, an increasing number of large genomic rearrangements have been detected. Here, we describe the characterization of pathogenic deletions of exons 1a-2 of BRCA1 in six families using loss of heterozygosity, array comparative genomic hybridization, and sequence analyses. Two families harbor a 37 kb deletion starting in intron 2 of psi BRCA1, encompassing NBR2, and exons 1a-2 of BRCA1, while the other four families have an 8 kb deletion with breakpoints in intron 2 of NBR2 and intron 2 of BRCA1. This observation, together with the previously described families with exon 1a-2 deletions of BRCA1, demonstrates that this type of deletions is relatively frequent in breast/ovarian cancer families.