title: The P1812A and P25T BRCA1 and the 5164del4 BRCA2 mutations: occurrence in high-risk non-Ashkenazi Jews.
abstract: Founder mutations in the BRCA1 and BRCA2 genes have been discovered in the Ashkenazic Jewish population, but a founder mutation(s) has not been discovered among non-Ashkenazi Jews (NAJ). Two BRCA1 mutations (P1812A, P25T), and a BRCA2 mutation (5164del4) have been detected in NAJ high-risk families. We studied the prevalence of these three mutations in 270 high-risk NAJ families, including 85 from Iraq/Iran, 67 from North Africa, 27 from Yemen, 50 from the Balkan region, and 41 with mixed ancestry. The three mutations were detected only in individuals related to the original families. We conclude that the P1812A and P25T BRCA1 and 5164del4 BRCA2 mutations are not likely to be founder mutations in NAJ high-risk families. We also assessed the pathogenicity of the BRCA1 P1812A mutation in vitro using reporter gene assays in yeast and mammalian cells. We found that the BRCA1 P1812A variant activity assays yielded a slightly reduced reporter gene activity. Thus, there is some uncertainty as to the pathogenicity of BRCA1 P1812A.
authors.affiliation: Oncology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Kaufman
authors.forename: Yael
authors.initials: Y
authors.lastname: Laitman
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Carvalho
authors.forename: Limor
authors.initials: L
authors.lastname: Edelman
authors.forename: Tal Distelman
authors.initials: TD
authors.lastname: Menachem
authors.forename: Jamal
authors.initials: J
authors.lastname: Zidan
authors.forename: Alvaro N
authors.initials: AN
authors.lastname: Monteiro
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000368:Aged; D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D011392:Proline / Q000235:genetics; D017384:Sequence Deletion; D013912:Threonine / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D013912:Threonine; D011392:Proline; D000409:Alanine