A NOVEL BRCA1 MUTATION IN AN IDENTICAL TWIN PAIR WITH SIMILAR CLINICAL HISTORIES

Factors affecting the penetrance and expression of BRCA1 are not under stood. Breast cancer risk and ovarian cancer risk, in general, are kno wn to be associated with non-Mendelian factors. However, whether and h ow these various factors influence tumor development in BRCA1 mutation carriers is not known. Here we report the breast and ovarian cancer s yndrome in an identical twin pair. These female identical twins had re markably similar clinical histories. Both twins developed histological ly similar ovarian cancer in their mid-fifties. One twin was diagnosed with stage III disease and died of refractory metastatic disease. The other twin was diagnosed with stage I disease but ultimately died of recurrent disease. Neither twin developed breast or colon cancer. The twins have both similarities and differences in terms of nongenetic ca ncer-related risk factors. Results of BRCA1 analysis of DNA from both twins revealed a novel mutation, 2711delA, which resulted in a prematu re termination at condon 892. This report has intriguing implications concerning the role of genotype in the ultimate penetrance and express ion of disease among BRCA1 mutation carriers. (C) Elsevier Science Inc ., 1998.