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BRCA1 5272‐1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin
Author(s) -
Infante M,
Durán M,
Acedo A,
PérezCabornero L,
Sanz DJ,
GarcíaGonzález M,
Beristain E,
EstebanCardeñosa E,
De La Hoya M,
Teulé A,
Vega A,
Tejada MI,
Lastra E,
Miner C,
Velasco EA
Publication year - 2010
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2009.01272.x
Subject(s) - founder effect , genetic counseling , genetics , ovarian cancer , biology , haplotype , mutation , breast cancer , allele , cancer , gene
Infante M, Durán M, Acedo A, Pérez‐Cabornero L, Sanz DJ, García‐González M, Beristain E, Esteban‐Cardeñosa E, de la Hoya M, Teulé A, Vega A, Tejada M‐I, Lastra E, Miner C, Velasco EA. BRCA1 5272‐1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin. 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 (∼380 years). A conserved haplotype associated to 5374delTATG was observed in four markers (0.82 Mb). The mutation occurred approximately 48 generations ago (∼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.