Female with both a BRCA1 and BRCA2 mutation
Germline mutations in the BRCA1 and BRCA2 genes infer an increased risk of breast/ovarian cancer. The co-existence of independent mutations in both genes in an individual is uncommon. This case reports a family where our patient, the proband, was found to have both a BRCA1 and BRCA2 mutation. The proband is a Caucasian female who was diagnosed with unilateral breast cancer at age 33. Her mother had unilateral breast cancer at age 61 and maternal grandmother had ovarian cancer in her early 40s. Both these relatives are deceased. Following two genetic counselling sessions the proband consented to BRCA analysis which revealed two mutations. PCR and DHPLC analysis confirmed that the proband had a single BRCA1 3819delGTAAA mutation (described in the BIC database as a deleterious frameshift mutation). PCR and sequence analysis confirmed that the proband also had a single BRCA2 IVS8+1G>A sequence variant. This change alters a highly conserved consensus splice sequence and is therefore likely to be a deleterious mutation. Genetic testing was offered and agreed to by the proband’s father though neither mutation was found in this relative. The proband has gone on to have further follow up counselling with our service and predictive genetic testing has been offered to the proband’s siblings.