title: The c.156_157insAlu BRCA2 rearrangement accounts for more than one-fourth of deleterious BRCA mutations in northern/central Portugal.
abstract: We evaluated the contribution of an Alu insertion in BRCA2 exon 3 (c.156_157insAlu) to inherited predisposition to breast/ovarian cancer in 208 families originated mostly from northern/central Portugal. We identified the c.156_157insAlu BRCA2 mutation in 14 families and showed that it accounts for more that one-fourth of deleterious BRCA1/BRCA2 mutations in breast/ovarian cancer families originated from this part of the country. This mutation originates BRCA2 exon 3 skipping and we demonstrated its pathogenic effect by showing that the BRCA2 full length transcript is derived only from the wild type allele in carriers, that it is absent in 262 chromosomes from healthy blood donors, and that it co-segregates with the disease. Polymorphic microsatellite markers were used for haplotype analysis in three informative families. In two of the three families one haplotype was shared for all but two markers, whereas in the third family all markers telomeric to BRCA2 differed from that observed in the other two. Although the c.156_157insAlu BRCA2 mutation has so far only been identified in Portuguese breast/ovarian cancer families, screening of this rearrangement in other populations will allow evaluation of whether or not it is a population-specific founder mutation and a more accurate estimation of its distribution and age.
authors: Department of Genetics, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.
authors: Ana
authors: A
authors: Peixoto
authors: Catarina
authors: C
authors: Santos
authors: Patrícia
authors: P
authors: Rocha
authors: Manuela
authors: M
authors: Pinheiro
authors: Sofia
authors: S
authors: Príncipe
authors: Deolinda
authors: D
authors: Pereira
authors: Helena
authors: H
authors: Rodrigues
authors: Fernando
authors: F
authors: Castro
authors: Joaquim
authors: J
authors: Abreu
authors: Leonor
authors: L
authors: Gusmão
authors: António
authors: A
authors: Amorim
authors: Manuel R
authors: MR
authors: Teixeira
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics; D011174:Portugal
chemical_list: D024682:BRCA2 Protein