BRCA1 founder mutations unique to South Africa: Genealogical identification of founding couples
A number of important genes are known to be involved in inherited susceptibility to breast and/or ovarian cancer. In the context of high-risk families, the most important genes are BRCA1 and BRCA2. Germ-line mutations within BRCA1 are responsible for different proportions of inherited susceptibility to breast/ovarian cancer, and the mutation spectrum within this gene is often unique to certain populations, such as the South African Afrikaner. Mutation analysis revealed two recurrent and unique BRCA1 mutations within this population group, namely the novel E881X and 1493delC mutations. A collaborative study was undertaken in order to define more precisely the proportion of Afrikaner families carrying these two BRCA1 mutations. We screened 146 South African Afrikaner breast and/or ovarian cancer families (selection based on three or more affected individuals) for the presence of these two founder mutations, E881X and 1493delC. Mutation identification was done by means of PCR-based mutation detection assays. Twenty-four families (16.44%) were identified harboring either of these disease-causing mutations. Seventeen of the families (11.64%) carried the E881X mutation whereas the 1493delC mutation was observed in seven (4.79%). Thus collectively, the two founder mutations accounted for ~ 17 % of Afrikaner breast cancer families, allowing for improved population-specific screening options. Genotype analyses indicated that these patients shared common ancestors. Using genealogical studies, the founding couples for these two mutations were revealed. All of whom arrived in the Cape during the late 1600s. Results regarding mutation analysis, genotyping and genealogy will be presented and discussed.