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Founder BRCA1/2 mutations in the Europe: France

Posted Aug 04 2010 1:14pm

In France geographical clustering in North-Eastern part is evident for two recurrent BRCA1 mutations, suggesting a founder effect. The c.3481_3491del11 (BIC: 3600del11) in exon 11 accounts for 37% and the nonsense mutation c.5128G>T (BIC: 5247G>T/Gly1710X) in exon 18 for 15% of all BRCA1/2 mutations in that region (overall 52%) [ 4 , 75 ].

The haplotype analysis of the families carrying the mutation c.3481_3491del11, all originating from Alsace–Lorraine, revealed the presence of a common allele, indicating a founder effect [ 75 ]. Although this mutation is found in many different geographical areas, it is more common in France. The BRCA1 mutation c.5128G>T would appear to be specific to the France, but the analysis of its haplotype is less conclusive and needs further confirmation [ 6 ].

The BRCA1 c.5030_5033delCTAA (BIC: 5149delCTAA) [ 76 ] and c.3839_3843delinsAGGC (BIC: 3958delCTCAGinsAGGC) [ 77 ] mutations were reported in at least three independent families from France.

Well-described founder mutations are identified in French-Canadians population in Quebec, which originated from France during 17–18th century settlement period. In this region 4 BRCA1 gene mutations (c.4327C>T (BIC: 4446C>T/Arg1443X), c.3756_3759del4 (BIC: 3875delGTCT), c.962G>A (BIC: 1081G>A), c.2834_2836delinsC (BIC: 2953delGTA/insC) and 3 BRCA2 mutations (c.3170_3174del5 (BIC: 3398del5), c.5857G>T (BIC: 6085G>T), c.8537_8538delAG (BIC: 8765delAG)) are now routinely included in early onset breast/ovarian cancer screening assays and represent up to 84% of the total BRCA1/2 mutations in the French-Canadian population in Quebec [ 78 ]. Among these, the most common founder mutations are BRCA1 c.4327C>T and BRCA2 c.8537_8538delAG and c.3170_3174del5, which are found in 1.7% of women affected by breast cancer diagnosed before age 41 and in 1.3% of women with ovarian cancer [ 6 ].

My full review article: Janavicius R. Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control


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