title: Identification of a founder BRCA2 mutation in Sardinian breast cancer families.
abstract: The population of Sardinia is characterized by a relatively low level of genetic heterogeneity: therefore 'founder mutations' can be expected to be found. We analysed 17 probands from families with high incidence of breast cancer or breast and ovarian cancer by sequencing the full-length coding regions of BRCA1 and BRCA2 genes. A novel BRCA2 frame-shift mutation, 3951del3insAT, which produces a protein truncated at codon 1258, was observed in six patients with BC from the same village. The mutation was not found in unaffected females (matched on basis of ethnicity and age) with no family history of cancer. Haplotype analysis strongly suggests that all affected persons had a common ancestor. The identification of this clinically significant founder mutation may facilitate screening/testing for inherited risk of breast cancer.
authors.affiliation: Centro di Diagnostica Biomolecolare e Citogenetica Emato-Oncologica, San Francesco Hospital, ASL3 via Mannironi 1, 08100 Nuoro, Italy. labematologia.nuoro@tiscali.it
authors.forename: Maria
authors.initials: M
authors.lastname: Monne
authors.forename: Giovanna
authors.initials: G
authors.lastname: Piras
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fancello
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Santona
authors.forename: Antonella
authors.initials: A
authors.lastname: Uras
authors.forename: Gennaro
authors.initials: G
authors.lastname: Landriscina
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mastio
authors.forename: Attilio
authors.initials: A
authors.lastname: Gabbas
mesh_terms: D000328:Adult; D000368:Aged; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D005260:Female; D018703:Founder Effect; D016368:Frameshift Mutation; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016609:Neoplasms, Second Primary / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology / Q000235:genetics; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: D024682:BRCA2 Protein