A novel mutation in the BRCA1 gene in an Iranian family with hereditary breast cancer

Breast cancer (B.C) is the most common female malignancy and is the major cause of death in middle-aged women. Therefore, early detection can play an important role in disease prevention. About 5 to 10% of the cases are due to an inherited mutation in two major genes, BRCA1and BRCA2 which transmits as an autosomal dominant form. Genetic testing enables us identifying patients at increased risk of developing B.CThe aim of the study was to identify the causative mutation of early B.C in a family with 9 affected members.Methods Linkage analysis was performed with the help of STR markers linked the BRCA1 and BRCA2 genes to indirectly track the mutation. Then the candidate gene was subsequently sequenced to find the mutation.Results Linkage analysis showed that BRCA1 gene is segregating with the disease. Sequencing results showed a novel heterozygote (c.3607 C> T, P.R1203 X) variant in BRCA1 gene. The variant was heterozygote in all affected members and was not present in healthy members of the family.Conclusions The newly identified variant caused a truncated protein which is not active and cause disease. Genetic testing is useful for the preventive interventions for families with high risk of the disease. Identification of these novel mutations helps in developing a mutation to program for early breast cancer screening. Early-onset B.C (less than 45 years) and a limited family history are sufficient to justify mutation screening with a detection rate of over 25% in this group.

Keywords:

breast cancer , BRCA1 gene , sequenceing , Iran