Two BRCA1/2 founder mutations in Jews of Sephardic origin.
Founder mutations in BRCA1/2 genes have been detected in several Jewish communities in Israel, including in Ashkenazi Jews and Jews who immigrated to Israel from Iraq, Yemen, Iran and Afghanistan. We analyzed DNA samples of patients of Sephardic origin (descendents of Jews from the Iberian Peninsula) with breast cancer (BC) and/or ovarian cancer (OC) and additional family history of these cancers. In this study we identified 2 mutations: p.A1708E in BRCA1 and c.67 + 1G > A (IVS2 + 1G > A) in BRCA2, each in 3 unrelated patients. The frequency of the two mutations was 26-31% among Sephardic high risk families and about 3% among the full cohort of 177 patients of this origin who were tested in our center. Based on haplotype analysis we concluded that these mutations are most probably founder mutations in Sephardic Jews. We recommend testing the two mutations in women of Sephardic origin who apply for BRCA testing because of personal and/or family history of BC and/or OC. Furthermore, we suggest adding them to the 5 mutations included in "The Jewish panel" of BRCA1/2 mutations that are being tested in Israel.
Department of Human Genetics & Metabolic Diseases, Hadassah Hebrew University Medical Center, Jerusalem, 91120, Israel. msagi@hadassah.org.il
Michal
M
Sagi
Avital
A
Eilat
Liat
L
Ben Avi
Yael
Y
Goldberg
Dani
D
Bercovich
Tamar
T
Hamburger
Tamar
T
Peretz
Israela
I
Lerer
D000328:Adult; D000352:Africa, Northern; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008877:Middle East; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D012307:Risk Factors; D055815:Young Adult
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human