title: The Tyr978X BRCA1 Mutation in Non-Ashkenazi Jews: Occurrence in High-Risk Families, General Population and Unselected Ovarian Cancer Patients.
abstract: Background: In Jewish individuals of Ashkenazi (East European) decent, three predominant mutations, 185 delAG and 5382insC (BRCA1) and 6174delT (BRCA2), seem to account for a substantial portion of germline mutations in high-risk breast/ovarian cancer families. Among non-Ashkenazi Jews, the 185delAG and the Tyr978X mutations, as well as several 'private' mutations have been reported within the BRCA1 gene. Objective: Assessing the occurrence rate of the Tyr978X BRCA1 germline mutation in Jewish non-Ashkenazi individuals: high-risk familial cases, unselected ovarian cancer patients and the general average risk Jewish Iraqi population. In addition, finding proof that this is a founder mutation. Methods: PCR amplification of the relevant fragment of the BRCA1 gene from constitutional DNA followed by restriction enzyme digest that differentiates the wild type from the mutant allele. In addition, BRCA1-linked markers were used for haplotype analysis. Results: The Tyr978X BRCA1 mutation was detected in 3/289 (1%) of the average-risk Jewish Iraqi population, in 7/408 (1.7%) high-risk Jewish non-Ashkenazi individuals (representing 332 unrelated families) and in 1/81 (1.2%) of unselected Jewish non-Ashkenazi ovarian cancer patients. Allelotyping using BRCA1-linked markers revealed an identical allelic pattern in all mutation carriers with the intragenic markers. Conclusions: Our findings suggest that this mutation is prevalent in Iraqi Jews, represents a founder mutation, and should be incorporated into the panel of mutations analyzed in high-risk families of the appropriate ethnic background. Copyright 2001 S. Karger AG, Basel
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Genetics, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: R.
authors.initials: R
authors.lastname: Shiri-Sverdlov
authors.forename: R.
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.forename: G.
authors.initials: G
authors.lastname: Ichezkel-Hirsch
authors.forename: W.H.
authors.initials: WH
authors.lastname: Gotlieb
authors.forename: R.
authors.initials: R
authors.lastname: Bruchim Bar-Sade
authors.forename: A.
authors.initials: A
authors.lastname: Chetrit
authors.forename: S.
authors.initials: S
authors.lastname: Rizel
authors.forename: B.
authors.initials: B
authors.lastname: Modan
authors.forename: E.
authors.initials: E
authors.lastname: Friedman