BACKGROUND: The Tyr978X BRCA1 mutation is a founder mutation detected in high-risk Iraqi-Iranian Jewish families as well as in the general non-Ashkenazi population. The same mutation was also reported in non-Jewish high-risk women from Canada. Its occurrence in non-Jewish individuals from Iran has never been tested. OBJECTIVE: Assess the occurrence rate of Tyr978X BRCA1 germline mutation in the general population of Iranian non- Jewish individuals and compare the BRCA1-linked haplotype of Jewish and non-Jewish mutation carriers. METHODS: PCR amplification of the relevant fragment of the BRCA1 gene, followed by restriction enzyme digestion that differentiates wild type from mutant allele. For haplotyping, 7 BRCA1-linked markers were used. The tested population included 442 apparently healthy Iranian non-Jewish individuals, and 17 mutation carriers from Israel and Canada. RESULTS: The Tyr978X BRCA1 mutation was not detected in any Iranian non-Jewish individual. The intragenic haplotype of all Jewish Israeli mutation carriers was identical, but differed from that of Canadian non-Jews in two intragenic markers. CONCLUSIONS: The Tyr978X BRCA1 mutation which is a founder mutation in Jews, may be a hot spot in non-Jewish high risk women, and probably does not represent a rare sequence variant in Iranian non-Jews.
Quintana-Murci, L., Gal, I., Bakhan, T., Quach, H., Sayar, S. H., Shiri-Sverdlov, R., Baruch, R. G., McElreavey, K., Dagan, E., Narod, S., & Friedman, E. (2005). The Tyr978X BRCA1 mutation: occurrence in non-Jewish Iranians and haplotype in French-Canadian and non-Ashkenazi Jews. Familial Cancer, 4(2), 85-88. https://doi.org/10.1007/s10689-004-2101-z