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.