title: Novel BRCA1 deleterious mutation (c.1918C>T) in familial breast and ovarian cancer syndrome who share a common ancestry.
abstract: Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA repair processes resulting in elevated genome instability and predisposing to breast and ovarian cancer. We report a novel mutation (c.1918C>T) in the exon 11 of the BRCA1 gene that consists of a nonsense mutation that causes a stop codon downstream in the 640 position of the protein. The mutation was present in two Spanish unrelated families and was associated with four breast cancer cases, including two bilateral breast cancer (one of them synchronous). The median age/mean age (range) was 48.5/44.25 years (27-53). This finding led us to perform haplotype analysis in all family carriers. Four highly polymorphic microsatellite markers were used (17-3858, 17-3930, D17S855, D17S1326) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common haplotype. None of the noncarriers of the mutation or of the 24 healthy controls showed this haplotype. Therefore, the c.1918C>T mutation carriers from these two families allows us to assert that all analyzed mutation carriers share a common ancestry.
authors.affiliation: Genetic Diagnostic Laboratory, University Hospital Virgen de la Arrixaca, Carretera Madrid-Cartagena s/n, 30120, El Palmar, Murcia, Spain, xgabaldo83@gmail.com.
authors.forename: Xavier
authors.initials: X
authors.lastname: Gabaldó Barrios
authors.forename: María Desamparados
authors.initials: MD
authors.lastname: Sarabia Meseguer
authors.forename: José Luis
authors.initials: JL
authors.lastname: Alonso Romero
authors.forename: Miguel
authors.initials: M
authors.lastname: Marín Vera
authors.forename: Gema
authors.initials: G
authors.lastname: Marín Zafra
authors.forename: Pilar
authors.initials: P
authors.lastname: Sánchez Henarejos
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Sánchez Bermúdez
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz Espejo
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D018389:Codon, Nonsense