+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin



BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin



Clinical Genetics 77(1): 60-69



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.

(PDF emailed within 0-6 h: $19.90)

Accession: 051744293

Download citation: RISBibTeXText

PMID: 19912264

DOI: 10.1111/j.1399-0004.2009.01272.x


Related references

High frequency of pathogenic non-founder germline mutations in BRCA1 and BRCA2 in families with breast and ovarian cancer in a founder population. Hereditary Cancer in Clinical Practice 16: 12-12, 2018

Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families. Journal of Medical Genetics 39(8): 611-614, 2002

Fifty percent of Jewish high-risk breast and ovarian cancer families are not explained by the three known BRCA1 or BRCA2 founder mutations while a 07 percent combined BRCA1 founder mutation frequency is reported in a Jewish cohort. American Journal of Human Genetics 59(4 SUPPL ): A28, 1996

Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: Implications for genetic testing. International Journal of Cancer 97(4): 466-471, 1 February, 2002

Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. Human Mutation 22(4): 301-312, 2003

Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. Journal of Medical Genetics 51(2): 98-107, 2014

Differences in the frequency and distribution of BRCA1 and BRCA2 mutations in breast/ovarian cancer cases from the Basque country with respect to the Spanish population: implications for genetic counselling. Breast Cancer Research and Treatment 106(2): 255-262, 2007

Founder BRCA1 and BRCA2 mutations in French Canadian breast and ovarian cancer families. American Journal of Human Genetics 63(5): 1341-1351, 1998

Founder BRCA1 mutations and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from North-Eastern Poland. Human Mutation 15(5): 480-481, 2000

Ashkenazi founder BRCA1/BRCA2 mutations in Slovak hereditary breast and/or ovarian cancer families. Neoplasma 53(2): 97-102, 2006

Prevalence of BRCA1 and BRCA2 founder mutations in Brazilian hereditary breast and ovarian cancer families. Journal of Clinical Oncology 26(15_suppl): 22108-22108, 2016

Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. American Journal of Human Genetics 60(5): 1059-1067, 1997

Founder mutations of BRCA1 and BRCA2 in North American families of Polish origin that are affected with breast cancer. American Journal of Human Genetics 68(2): 546-546, 2001

The limited spectrum of pathogenic BRCA1 and BRCA2 mutations in the French Canadian breast and breast-ovarian cancer families, a founder population of Quebec, Canada. Bulletin du Cancer 93(9): 841-846, 2006

Screening for BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50, and CDH1 mutations in high-risk Finnish BRCA1/2-founder mutation-negative breast and/or ovarian cancer individuals. Breast Cancer Research 13(1): R20-R20, 2014