Editor—About 3-10% of breast cancer cases have been estimated to result from a hereditary susceptibility to the disease.1 A significant proportion of these are the result of mutations in the BRCA1 gene.2 While several hundred BRCA1 gene mutations have been identified, the disease causing effect of some BRCA1 variants is a matter of current debate. In a recent issue of this journal, a 12 bp duplication in intron 20 of the BRCA1 gene has been proposed to be a regulatory mutation.3 This intronic variant had initially been described in a North American patient and was tentatively classified as a splicing mutation.2 4 It has also been detected in a population based sample of young breast cancer patients and was suggested to affect mRNA processing.5 In another study of Polish patients, a splicing effect was excluded but mRNA reduction has been suggested as a possible consequence of the variant.6 Robledoet al 3 provided experimental evidence to suggest that the intronic 12 bp duplication could act as a regulatory mutation resulting in the allele specific reduction of BRCA1 expression,3 although the underlying mechanism for such an effect remained unclear. Here we have investigated the expression of BRCA1 mRNA transcribed from the allele carrying the 12 bp duplication and provide evidence against a regulatory effect of this variant.

We have screened genomic PCR products …