title: A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families.
abstract: We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian hereditary breast and ovarian cancer families collected either for research or for clinical diagnostic purposes. Twenty-eight distinct mutations have been observed, 18 of them not previously reported and 12 of them occurring more than once. Most conspicuously, a 2804delAA mutation has been found 19 times and has never been reported outside the Netherlands. A common haplotype spanning > or = 375 kb could be identified for each of the nine examined recurrent mutations, indicating the presence of multiple BRCA1 founder mutations in the Dutch population. The 2804delAA mutation has been estimated to have originated approximately 32 generations ago. No specific breast or ovarian cancer phenotype could be assigned to any of the common mutations, and the ovarian cancer incidence among 18 families with the 2804delAA mutation was heterogeneous.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Peelen
authors.forename: M
authors.initials: M
authors.lastname: van Vliet
authors.forename: A
authors.initials: A
authors.lastname: Petrij-Bosch
authors.forename: R
authors.initials: R
authors.lastname: Mieremet
authors.forename: C
authors.initials: C
authors.lastname: Szabo
authors.forename: A M
authors.initials: AM
authors.lastname: van den Ouweland
authors.forename: F
authors.initials: F
authors.lastname: Hogervorst
authors.forename: R
authors.initials: R
authors.lastname: Brohet
authors.forename: M J
authors.initials: MJ
authors.lastname: Ligtenberg
authors.forename: E
authors.initials: E
authors.lastname: Teugels
authors.forename: R
authors.initials: R
authors.lastname: van der Luijt
authors.forename: A H
authors.initials: AH
authors.lastname: van der Hout
authors.forename: J J
authors.initials: JJ
authors.lastname: Gille
authors.forename: G
authors.initials: G
authors.lastname: Pals
authors.forename: I
authors.initials: I
authors.lastname: Jedema
authors.forename: R
authors.initials: R
authors.lastname: Olmer
authors.forename: I
authors.initials: I
authors.lastname: van Leeuwen
authors.forename: B
authors.initials: B
authors.lastname: Newman
authors.forename: M
authors.initials: M
authors.lastname: Plandsoen
authors.forename: M
authors.initials: M
authors.lastname: van der Est
authors.forename: G
authors.initials: G
authors.lastname: Brink
authors.forename: S
authors.initials: S
authors.lastname: Hageman
authors.forename: P J
authors.initials: PJ
authors.lastname: Arts
authors.forename: M M
authors.initials: MM
authors.lastname: Bakker
authors.forename: P
authors.initials: P
authors.lastname: Devilee
mesh_terms: D000328:Adult; D001530:Belgium / Q000453:epidemiology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D019398:Genes, BRCA1; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype