International distribution and age estimation of the Portuguese BRCA2 c.156-157insAlu founder mutation

Ana Peixoto, Catarina Santos, Manuela Pinheiro, Pedro Pinto, Maria José Soares, Patrícia Rocha, Leonor Gusmão, António Amorim, Annemarie Van Der Hout, Anne Marie Gerdes, Mads Thomassen, Torben A. Kruse, Dorthe Cruger, Lone Sunde, Yves Jean Bignon, Nancy Uhrhammer, Lucie Cornil, Etienne Rouleau, Rosette Lidereau, Drakoulis YannoukakosMaroulio Pertesi, Steven Narod, Robert Royer, Maurício M. Costa, Conxi Lazaro, Lidia Feliubadaló, Begoña Graña, Ignacio Blanco, Miguel De La Hoya, Trinidad Caldés, Philippe Maillet, Gaelle Benais-Pont, Bruno Pardo, Yael Laitman, Eitan Friedman, Eladio A. Velasco, Mercedes Durán, Maria Dolores Miramar, Ana Rodriguez Valle, María Teresa Calvo, Ana Vega, Ana Blanco, Orland Diez, Sara Gutiérrez-Enríquez, Judith Balmaña, Teresa Ramon Y Cajal, Carmen Alonso, Montserrat Baiget, William Foulkes, Marc Tischkowitz, Rachel Kyle, Nelly Sabbaghian, Patricia Ashton-Prolla, Ingrid P. Ewald, Thangarajan Rajkumar, Luisa Mota-Vieira, Giuseppe Giannini, Alberto Gulino, Maria I. Achatz, Dirce M. Carraro, Brigitte Bressac De Paillerets, Audrey Remenieras, Cindy Benson, Silvia Casadei, Mary Claire King, Erik Teugels, Manuel R. Teixeira

Research output: Contribution to journalArticlepeer-review


The c.156-157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,443 suspected HBOC families from several countries. Whereas the c.156-157insAlu BRCA2 mutation was detected in 11 of 149 suspected HBOC families from Portugal, representing 37.9% of all deleterious mutations, in other countries it was detected only in one proband living in France and in four individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 ± 215 years ago. We further demonstrate significant quantitative differences regarding the production of the BRCA2 full length RNA and the transcript lacking exon 3 in c.156-157insAlu BRCA2 mutation carriers and in controls. The cumulative incidence of breast cancer in carriers did not differ from that of other BRCA2 and BRCA1 pathogenic mutations. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement.

Original languageEnglish
Pages (from-to)671-679
Number of pages9
JournalBreast Cancer Research and Treatment
Issue number3
Publication statusPublished - Jun 2011


  • Age estimation
  • c.156-157insAlu BRCA2 mutation
  • Founder mutation
  • Hereditary breast/ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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