In 517 Dutch families at a family @entity5 clinic, we screened for @entity6069 alterations using the Protein Truncation Test (PTT) covering approximately 60% of the coding sequences of both genes and direct testing for a number of previously identified Dutch recurrent mutations. In 119 (23%) of the 517 families, we detected a mutation in @entity5345 (n=98; 19%) or @entity2674 (n=21; 4%). @entity6069 mutations were found in 72 (52%) of 138 families with @entity5344 (HBOC), in 43 (13%) of the 339 families with @entity0 only (HBC), in 4 (36%) of 11 families with @entity43 only (HOC), and in nine of 29 families with one single young case (<40 years) of @entity0 . Between the different subgroups of families (subdivided by the number of @entity1 , @entity5 phenotype and age of onset) the proportion of @entity6069 mutations detected, varied between 6 and 82%. Eight different mutations, each encountered in at least six distinct families, represented as much as 61% (73/119 families) of all mutations found. The original birthplaces of the ancestors of carriers of these eight recurrent mutations were traced. To estimate the relative contribution of two important regional recurrent mutations ( @entity5345 founder mutation @entity70357 and @entity2674 founder mutation @entity70358 ) to the overall occurrence of @entity0 , we performed a population-based study in two specific small regions. The two region-specific @entity5345 and @entity2674 founder mutations were detected in 2.8% (3/106) and 3.2% (3/93) of the unselected @entity0 , respectively. Of @entity5 diagnosed before the age of 50 years, 6.9% (3/43) and 6.6% (2/30) carried the region-specific founder mutation. Thus, large regional differences exist in the prevalence of certain specific @entity5345 / @entity2674 founder mutations, even in very small areas concerning populations of approximately 200000 inhabitants.

Large regional differences in the frequency of distinct @entity5345 / @entity2674 mutations in 517 Dutch XXXX families.

@entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian cancer'] @entity1 :: ('9606', 'Species') :: ['patients'] @entity5344 :: ('MESH:D061325', 'Disease') :: ['breast and ovarian cancer'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'breast tumours'] @entity70357 :: ('c|DEL|IVS12-1643|3835', 'DNAMutation') :: ['IVS12-1643del3835'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer', 'tumours'] @entity5345 :: ('672', 'Gene') :: ['BRCA1'] @entity2674 :: ('675', 'Gene') :: ['BRCA2'] @entity70358 :: ('c|INS|5579|A', 'DNAMutation') :: ['5579insA'] @entity6069 :: ('672;675', 'Gene') :: ['BRCA1/2']
@entity5344 :: (MESH:D061325,Disease) :: ['breast and/or ovarian cancer']
