Abstract
Mutations in the BRCA1 and BRCA2 genes increase the risk for various cancers including breast, ovarian, prostate, pancreas and melanoma. Identifying BRCA1/2 mutation carriers enables risk assessment, surveillance, early detection and risk reduction. In certain Israeli sub-populations recurring and founder mutations have been identified and for these, testing for founder mutations is simple, efficient and cost-effective. Founder mutations in the Jewish Ethiopian population have not been described. We report here the identification of a recurring BRCA2 mutation in the Ethiopian Jewish population; c.5159C>A; p.Ser1720Ter, which has only been described once before in this population. In addition, in another family of the same origin we found the BRCA2 c.7579delG; p.Val2527Ter mutation that has been previously described in two different Jewish Ethiopian families. In Israel genetic testing is performed in a sequential stepwise manner, first testing a panel of predominant mutations and if negative further testing by gene sequencing is offered. Recently it has been decided to expand the founder mutation panel to include mutations which have been found in two or more separate families. This new panel will include the BRCA2 c.7579delG; p.Val2527Ter mutation, and we recommend that the BRCA2 c.5159C>A; p.Ser1720Ter mutation should also be added to the new predominant mutation panel.
This is a preview of subscription content, log in via an institution to check access.
References
Bernstein-Molho R, Laitman Y, Schayek H, Reish O, Lotan S, Haim S, Zidan J, Friedman E (2018) The yield of targeted genoty** for the recurring mutations in BRCA1/2 in Israel. Breast Cancer Res Treat 167(3):697–702. https://doi.org/10.1007/s10549-017-4551-7
Barnes-Kedar I, Bernstein-Molho R, Ginzach N, Hartmajer S, Shapira T, Magal N, Kalis ML, Peretz T, Shohat M, Basel-Salmon L, Friedman E, Bazak L, Goldberg Y (2018) The yield of full BRCA1/2 genoty** in Israeli high-risk breast/ovarian cancer patients who do not carry the predominant mutations. Breast Cancer Res Treat 172(1):151–157. https://doi.org/10.1007/s10549-018-4887-7
Bernstein-Molho R, Friedman E, Kedar I, Laitman Y, Allweis TM, Gal-Yam EN, Feldman HB, Grinshpun A, Halpern N, Hartmajer S, Kadouri L, Katz LH, Kaufman B, Laish I, Levanon K, Philipsborn SL, Ludman M, Moran G, Peretz T, Reinstein E et al (2020) Diagnostic yield of multigene panel testing in an Israeli cohort: enrichment of low-penetrance variants. Breast cancer research and treatment 181(2):445–453. https://doi.org/10.1007/s10549-020-05633-2
Central Bureau of Statistics, State of Israel (2020). The Population of Ethiopian Originin Israel. https://www.cbs.gov.il/he/mediarelease/DocLib/2020/358/11_20_358e.pdf
The Jewish Agency for Israel (2007). The Aliyah of the Ethiopian Jewish community. http://archive.jewishagency.org/he/historical-aliyah/content/22095
Association of Ethiopian Jews (2018). History of the Ethiopian Jewish community. Retrieved from https://www.iaej.co.il/%D7%A2%D7%9C-%D7%94%D7%A7%D7%94%D7%99%D7%9C%D7%94/%D7%94%D7%99%D7%A1%D7%98%D7%95%D7%A8%D7%99%D7%94/#2
Zoossmann-Diskin A, Ticher A, Hakim I, Goldwitch Z, Rubinstein A, Bonne-Tamir B (1991) Genetic affinities of Ethiopian Jews. Israel J Med Sci 27(5):245–251
Behar DM, Yunusbayev B, Metspalu M, Metspalu E, Rosset S, Parik J, Rootsi S, Chaubey G, Kutuev I, Yudkovsky G, Khusnutdinova EK, Balanovsky O, Semino O, Pereira L, Comas D, Gurwitz D, Bonne-Tamir B, Parfitt T, Hammer MF, Skorecki K et al (2010) The genome-wide structure of the Jewish people. Nature 466(7303):238–242. https://doi.org/10.1038/nature09103
Non AL, Al-Meeri A, Raaum RL, Sanchez LF, Mulligan CJ (2011) Mitochondrial DNA reveals distinct evolutionary histories for Jewish populations in Yemen and Ethiopia. Am J Phys Anthropol 144(1):1–10. https://doi.org/10.1002/ajpa.21360
Lovell A, Moreau C, Yotova V, **ao F, Bourgeois S, Gehl D, Bertranpetit J, Schurr E, Labuda D (2005) Ethiopia: between Sub-Saharan Africa and western Eurasia. Ann Hum Genet 69(Pt 3):275–287. https://doi.org/10.1046/j.1529-8817.2005.00152.x
Litz Philipsborn S, Hartmajer S, Shtorch Asor A, Vinovezky M, Regev M, Singer A, Reinstein E (2021) A Founder Mutation in TCTN2 Causes Meckel-Gruber syndrome type 8 among Jews of Ethiopian and Yemenite Origin. American journal of medical genetics, Part A (Printing)
Mandelker D, Zhang L, Kemel Y, Stadler ZK, Joseph V, Zehir A, Pradhan N, Arnold A, Walsh MF, Li Y, Balakrishnan AR, Syed A, Prasad M, Nafa K, Carlo MI, Cadoo KA, Sheehan M, Fleischut MH, Salo-Mullen E, Trottier M et al (2017) Mutation detection in patients with advanced cancer by universal sequencing of cancer-related genes in tumor and normal DNA vs guideline-based germline Testing. JAMA 318(9):825–835. https://doi.org/10.1001/jama.2017.11137
Weinberg-Shukron A, Rachmiel M, Renbaum P, Gulsuner S, Walsh T, Lobel O, Dreifuss A, Ben-Moshe A, Zeligson S, Segel R, Shore T, Kalifa R, Goldberg M, King MC, Gerlitz O, Levy-Lahad E, Zangen D (2018) Essential role of BRCA2 in ovarian development and function. N Engl J Med 379(11):1042–1049. https://doi.org/10.1056/NEJMoa1800024
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ludman, M.D., Philipsborn, S.L., Hartmajer, S. et al. Recurring pathogenic variants in the BRCA2 gene in the Ethiopian Jewish population. Founder mutations?. Familial Cancer 21, 121–123 (2022). https://doi.org/10.1007/s10689-021-00255-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-021-00255-z