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Two BRCA1/2 founder mutations in Jews of Sephardic origin

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Abstract

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.

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Acknowledgment

We wish to thank our dedicated nurse Ms. Michele Gordon for the support she has always given to our patients and Ms. Susan Mendelson for her technical assistance.

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Authors and Affiliations

  1. Department of Human Genetics & Metabolic Diseases, Hadassah Hebrew University Medical Center, Jerusalem, 91120, Israel

    Michal Sagi, Avital Eilat, Liat Ben Avi & Israela Lerer

  2. Sharett institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel

    Yael Goldberg, Tamar Hamburger & Tamar Peretz

  3. The Human Molecular Genetics, Migal - Galilee Bio-Technology Center, Kiryat-Shmona, Israel and Tel Hai Academic College, Tel Hai, Israel

    Dani Bercovich

Authors
  1. Michal Sagi
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  2. Avital Eilat
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  3. Liat Ben Avi
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  4. Yael Goldberg
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  5. Dani Bercovich
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  6. Tamar Hamburger
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  7. Tamar Peretz
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  8. Israela Lerer
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Correspondence to Michal Sagi.

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Sagi, M., Eilat, A., Ben Avi, L. et al. Two BRCA1/2 founder mutations in Jews of Sephardic origin. Familial Cancer 10, 59–63 (2011). https://doi.org/10.1007/s10689-010-9395-9

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  • DOI: https://doi.org/10.1007/s10689-010-9395-9

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