So, there is a suggestion that mutation in OCCR is less penetrate

So, there is a suggestion that mutation in OCCR is less penetrate for breast LY2874455 cancer at younger ages. In the current study, RAD001 in vitro the BRCA2 mutation in exon 9 is outside the

OCCR. This explains why all the Egyptian breast cancer patients having this mutation are of young age, less than forty. In our study, the identified repeated mutation in exon 13 of BRCA1 gene is a nonsense mutation (4446 C–T). It was detected in 20% of families. This mutation was found frequently in French-Canadian families and two families in France [35]. These multiple instances of mutation did not represent a founder effect many generations in the past. There was evidence for multiple independent BRCA1 mutational events and so multiple origins [41]. The 4446 C–T mutation is one of the most common mutations found in the Breast Cancer Information Core Data base. These mutations are likely to have arisen independently owing to the presence of mutational hot spots in the coding sequence of the gene [42]. The last investigated exon in BRCA1 gene see more for detection of mutation was exon 8. It has been found that 13.3% of index patients and half their asymptomatic relatives have mutation in exon 8(738 C–A). This mutation is a missense mutation predicted to destroy the protein ring-finger. Hamann et al. [37] found one missense mutation in exon 8 of BRCA1 gene in Germany.

Farnesyltransferase The coexistence of more than founder mutation has been reported in some Ashkenazi Jewish families [40]. In the current study, four families of the 60 Egyptian families were found to have inherited

mutation in both BRCA1 and BRCA2 genes, they are double heterozygote. Previous studies described an Ashkenazi Jewish patient found to have germline mutations in both BRCA1 and BRCA2 genes [43]. The potential explanation for the occurrence of the two mutations occurring in the same individual is that BRCA1 and BRCA2 have been implicated in the maintenance of genomic integrity [9, 11]. Collectively, it is obvious that BRCA1 and/or BRCA 2 mutations have been found to account for a greater proportion of breast cancer patients among the studied families. This observation might be due to the relatively young ages of diagnosis of breast cancer and that the hereditary cancers occur disproportionally in young women. The accumulation of BRCA1 and BRCA2 mutations data from sets of families revealed the prevalence of different mutations and the significance of the putative recurrent founder mutations in Egyptians. The high frequency of any recurrent mutation (frame shift), so far, suggest that there may be a strong BRCA1 and 2 founder effects in Egyptian population. The presence of putative founder mutations, which leading to reduce genetic heterogeneity of BRCA genes, facilitates carrier detection and genetic counseling.

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