A BRCA1 founder mutation, identified with haplotype analysis, allowing genotype/phenotype determination and predictive testing.

We searched for a founder mutation in a population from one geographic region of Norway with prevalent breast/ovarian cancer families. We sampled 33 breast/ovarian cancer families and determined haplotypes of four markers linked to the BRCA1 region. Of the affected 33 index women, 13 (39.4%) shared one haplotype. In five (15% of total), an identical mutation was indicated by an abnormal truncated protein test (PTT) of exon 11 and shown to represent a 1675delA mutation. In the other index women, PTT of exon 11 showed no abnormality. No other BRCA1 founder mutation of this prevalence is likely because no other haplotype was more frequent in affecteds than in controls. All families with the 1675delA mutation in this geographic region may be considered as part of one large kindred. This allows a genotype-phenotype correlation to be precisely determined and used in genetic counselling for predictive testing within this kindred. Identification of identical haplotypes between unrelated affected individuals may be used to estimate the extent of founder effects for any mapped disease, without knowledge of the specific founder mutation.