title: International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation.
abstract: 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.
authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, Porto 4200-072, Portugal.
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authors.forename: Begoña
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authors.forename: Mercedes
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authors.forename: Maria-Dolores
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authors.lastname: Miramar
authors.forename: Ana Rodriguez
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authors.forename: María-Teresa
authors.initials: MT
authors.lastname: Calvo
authors.forename: Ana
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authors.lastname: Vega
authors.forename: Ana
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authors.forename: Orland
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authors.lastname: Gutiérrez-Enríquez
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authors.lastname: Balmaña
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authors.lastname: Ramon y Cajal
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authors.lastname: Alonso
authors.forename: Montserrat
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authors.lastname: Baiget
authors.forename: William
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authors.lastname: Foulkes
authors.forename: Marc
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authors.lastname: Tischkowitz
authors.forename: Rachel
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authors.lastname: Kyle
authors.forename: Nelly
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authors.lastname: Sabbaghian
authors.forename: Patricia
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authors.lastname: Ashton-Prolla
authors.forename: Ingrid P
authors.initials: IP
authors.lastname: Ewald
authors.forename: Thangarajan
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authors.lastname: Rajkumar
authors.forename: Luisa
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authors.lastname: Mota-Vieira
authors.forename: Giuseppe
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authors.lastname: Giannini
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authors.lastname: Gulino
authors.forename: Maria I
authors.initials: MI
authors.lastname: Achatz
authors.forename: Dirce M
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authors.lastname: Carraro
authors.forename: Brigitte Bressac
authors.initials: BB
authors.lastname: de Paillerets
authors.forename: Audrey
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authors.lastname: Remenieras
authors.forename: Cindy
authors.initials: C
authors.lastname: Benson
authors.forename: Silvia
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authors.lastname: Casadei
authors.forename: Mary-Claire
authors.initials: MC
authors.lastname: King
authors.forename: Erik
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mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005828:Genetics, Population; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011174:Portugal / Q000453:epidemiology; D012333:RNA, Messenger / Q000032:analysis; D016364:Reading Frames / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D012333:RNA, Messenger