title: BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin.
abstract: The distribution of BRCA1 and BRCA2 germ line mutations in breast/ovarian cancer families varies among different populations, which typically present a wide spectrum of unique mutations. Splicing mutation 5272-1G>A of BRCA1 and frameshift mutation 5374delTATG of BRCA2 are highly prevalent mutations in Castilla-León (Spain), accounting for 18.4% and 13.6% of BRCA1 and BRCA2 positive families, respectively. To test the presence of founder effects, 9 Spanish 5272-1G>A and 13 5374delTATG families were genotyped with polymorphic markers linked to BRCA1 or BRCA2. All the 5272-1G>A families shared a common haplotype in eight markers (1.1 Mb region) and the mutation age was estimated in 15 generations (approximately 380 years). A conserved haplotype associated to 5374delTATG was observed in four markers (0.82 Mb). The mutation occurred approximately 48 generations ago (approximately 1200 years). Each mutation likely arose from a common ancestor that could be traced to a small area of Castilla-León and expanded to other Spanish regions. They can have a significant impact on the clinical management of asymptomatic carriers as well as on the genetic screening strategy to be followed in populations with Spanish ancestries.
authors.affiliation: Grupo de Genética del Cáncer, Instituto de Biología y Genética Molecular (UVa-CSIC), Valladolid.
authors.forename: M
authors.initials: M
authors.lastname: Infante
authors.forename: M
authors.initials: M
authors.lastname: Durán
authors.forename: A
authors.initials: A
authors.lastname: Acedo
authors.forename: L
authors.initials: L
authors.lastname: Pérez-Cabornero
authors.forename: D J
authors.initials: DJ
authors.lastname: Sanz
authors.forename: M
authors.initials: M
authors.lastname: García-González
authors.forename: E
authors.initials: E
authors.lastname: Beristain
authors.forename: E
authors.initials: E
authors.lastname: Esteban-Cardeñosa
authors.forename: M
authors.initials: M
authors.lastname: de la Hoya
authors.forename: A
authors.initials: A
authors.lastname: Teulé
authors.forename: A
authors.initials: A
authors.lastname: Vega
authors.forename: M-I
authors.initials: MI
authors.lastname: Tejada
authors.forename: E
authors.initials: E
authors.lastname: Lastra
authors.forename: C
authors.initials: C
authors.lastname: Miner
authors.forename: E A
authors.initials: EA
authors.lastname: Velasco
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion; D013030:Spain; D055815:Young Adult