Unique germline mutations in BRCA and BRCA2 account for inherited predisposition to breast and ovarian cancer in high-risk families.
In Jewish high-risk individuals of Ashkenazi (east European) descent, three predominant mutations, 185delAG and 5382insC (BRCA 1) and 6174delT (BRCA2), seem to account for a substantial portion of germline mutations, and two of these mutations (185delAG and 6174delT) are also found at about 1% each in the general Jewish-Ashkenazi population.
We identified a novel BRCA1 mutation in two Jewish-non-Ashkenazi families with ovarian cancer : a thymidine to guanidine alteration at position 3053, resulting in substitution of tyrosine at codon 1017 for a stop codon (Tyr1017Ter).
The mutation was first detected by protein truncation test (PTT) and confirmed by sequencing and a modified restriction digest assay.
Allelotyping of mutation carriers using intragenic BRCA 1 markers revealed that the haplotype was identical in these seemingly unrelated families.
No mutation carrier was found among 118 unselected Jewish individuals of Iranian origin.
Our findings suggest that this novel mutation should be incorporated into the panel of mutations analysed in high-risk families of the appropriate ethnic background, and that the repertoire of BRCA1 mutations in Jewish high-risk families may be limited, regardless of ethnic origin.
Mots-clés Pascal : Tumeur maligne, Ovaire, Mutation, Gène suppresseur tumeur, Haplotype, Juif, Ethnie, Dépistage, Israël, Asie, Autoradiographie, Homme, Appareil génital femelle pathologie, Ovaire pathologie, Génétique, Gène BRCA1
Mots-clés Pascal anglais : Malignant tumor, Ovary, Mutation, Tumor suppressor gene, Haplotype, Jew, Ethnic group, Medical screening, Israel, Asia, Autoradiography, Human, Female genital diseases, Ovarian diseases, Genetics
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 98-0297488
Code Inist : 002B20C02. Création : 27/11/1998.