Assessment of the prevalence of de novo mutations in the BRCA1 and BRCA2 genes.

To the Editor : In the 16 years since the discovery of BRCA1 and BRCA2, only one de novo mutation in the BRCA1 gene and four de novo mutations in the BRCA2 gene have been reported in the literature (1–5). No systematic study of de novo mutation prevalence has been performed. This is surprising, given that the rates of de novo mutations can be as high as 30–50% for genes such as NF1, RET, and APC (6–8). We conducted the present study in an attempt to evaluate the prevalence of de novo mutations in BRCA1 and BRCA2 in a clinic-based cohort of women seeking risk assessment. To our knowledge, this study is the first to systematically approach this question. Patients who would be most likely to carry de novo mutations in the BRCA1/2 genes were