IMPLICATIONS OF A NOVEL CRYPTIC SPLICE-SITE IN THE BRCA1 GENE

This study was designed to determine the significance of a single intr onic base change (IVS5 -12 G-->A) found in a family with a history of breast cancer. This change is predicted to form a cryptic splice site resulting in the addition of 11 nucleotides to the BRCA1 transcript. T he BRCA1 gene of the relatives and control individuals was sequenced a nd analyzed using RT-PCR, ASO hybridization, and size fractionation. A ll patients showed an 11 nucleotide insert at the intron 5/exon 6 boun dary. This variant is likely to form a short protein product incapable of the hypothesized tumor suppressor functions of the BRCA1 gene. Thi s information is important for providing counseling for families with this cryptic splice site and a family history of breast cancer. (C) 19 98 Wiley-Liss, Inc.