An unaffected individual from a breast/ovarian cancer family with germlinemutations in both BRCA1 and BRCA2

Currently many centers offer testing for three specific mutations, 185delAG , 5382insC, and 6174delT, in the BRCA1 and BRCA2 genes to Ashkenazi Jewish individuals at high risk for breast and ovarian cancer. We recently tested members of a family with multiple cases of breast and ovarian cancer (Famil y R014). The proband in this family tested positive for the 185delAG mutati on. The unaffected sister of the proband tested positive for both the 185de lAG and the 6174delT mutations, Further testing and review of the family hi story suggest that both mutations may have come from a maternal grandfather and passed down for two generations. Counseling of the unaffected double h eterozygote individual in this family is complicated by lack of information on the risk of breast, ovarian, and other cancers in such individuals. A b etter understanding of these risks will depend on the identification and st udy of more individuals carrying mutations in both the BRCA1 and BRCA2 gene s. Our study emphasizes the importance of testing Ashkenazi Jewish individu als from high-risk breast and ovarian cancer families for all three common BXCA1 and BRCA2 mutations identified in this ethnic group.