BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin.
Clin Genet
; 77(1): 60-9, 2010 Jan.
Article
en En
| MEDLINE
| ID: mdl-19912264
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Neoplasias de la Mama
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Efecto Fundador
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Genes BRCA1
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Genes BRCA2
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Asesoramiento Genético
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Europa
Idioma:
En
Año:
2010
Tipo del documento:
Article