A founder BRCA2 mutation in non-Afrikaner breast cancer patients of the Western Cape of South Africa

Authors

  • NC van der Merwe,

    Corresponding author
    1. Division of Human Genetics, University of the Free State, Bloemfontein, South Africa
    2. Department of Human Genetics, National Health Laboratory Services, Bloemfontein, South Africa
      Nerina van der Merwe, Division of Human Genetics, G11, PO Box 339, University of the Free State, Bloemfontein, South Africa.
      Tel.: +27 51 405 3351
      fax: +27 51 444 4195
      e-mail: vanderMerweNC@ufs.ac.za
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  • N Hamel,

    1. Research Institute of the McGill University Health Centre
    2. Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada
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  • S-R Schneider,

    1. Department of Human Genetics, National Health Laboratory Services, Bloemfontein, South Africa
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  • JP Apffelstaedt,

    1. Department of Surgery, University of Stellenbosch and Breast Clinic, Tygerberg Hospital, Cape Town, South Africa
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  • JT Wijnen,

    1. Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands
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  • WD Foulkes

    1. Research Institute of the McGill University Health Centre
    2. Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada
    3. Lady Davis Institute and Segal Cancer Centre, Jewish Hospital, Montréal, Quebec, Canada
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Nerina van der Merwe, Division of Human Genetics, G11, PO Box 339, University of the Free State, Bloemfontein, South Africa.
Tel.: +27 51 405 3351
fax: +27 51 444 4195
e-mail: vanderMerweNC@ufs.ac.za

Abstract

van der Merwe NC, Hamel N, Schneider S-R, Apffelstaedt JP, Wijnen JT, Foulkes WD. A founder BRCA2 mutation in non-Afrikaner breast cancer patients of the Western Cape of South Africa.

Founder mutations in BRCA1 and BRCA2 have been reported in many different populations. We studied 105 Coloured and 16 Black Xhosa women residing in the Western Cape of South Africa diagnosed with breast cancer. We screened these patients using our standard panel of six previously reported SA Afrikaner and Ashkenazi Jewish BRCA1/2 mutations and identified only two Afrikaner mutations. Further screening by the protein truncation test (BRCA1 exon 11, and BRCA2 exons 10 and 11) revealed an additional four deleterious mutations (BRCA1 c.1504_ 1508del,p.Leu502AlafsX2, BRCA2 c.2826_2829del,p.Ile943LysfsX16, c.6447_6448dup,p.Lys2150IlefsX19 and c.5771_5774del,p.Ile1924Argfs X38). The latter, also known in Breast Cancer Information Core nomenclature as 5999del4, was identified in 4 of 105 (3.8%) Coloureds and 4 of 16 (25%) Xhosa women, which makes it a frequent founder mutation in the Western Cape Province. Although this mutation was previously reported to occur in the Netherlands, haplotype analysis indicated two distinct origins for the Dutch and South African mutations, excluding the possibility of a common Dutch ancestor and suggesting gene flow from the indigenous tribes such as the Xhosa to the Coloured population instead. Further studies to determine the carrier rate of this variant in the Xhosa and other SA populations are warranted.

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