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A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51

Author

Listed:
  • Najim Ameziane

    (VU University Medical Center)

  • Patrick May

    (Luxembourg Centre for Systems Biomedicine, House of Biomedicine
    Institute for Systems Biology)

  • Anneke Haitjema

    (VU University Medical Center)

  • Henri J. van de Vrugt

    (VU University Medical Center
    The Netherlands Cancer Institute)

  • Sari E. van Rossum-Fikkert

    (Cancer Genomics Center
    Erasmus Medical Center)

  • Dejan Ristic

    (Cancer Genomics Center
    Erasmus Medical Center)

  • Gareth J. Williams

    (Lawrence Berkeley National Laboratory)

  • Jesper Balk

    (VU University Medical Center)

  • Davy Rockx

    (VU University Medical Center)

  • Hong Li

    (Institute for Systems Biology)

  • Martin A. Rooimans

    (VU University Medical Center)

  • Anneke B. Oostra

    (VU University Medical Center)

  • Eunike Velleuer

    (Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich Heine University)

  • Ralf Dietrich

    (Deutsche Fanconi-Anämie-Hilfe e.V.)

  • Onno B. Bleijerveld

    (Mass Spectrometry and Proteomics Facility, The Netherlands Cancer Institute)

  • A. F. Maarten Altelaar

    (Mass Spectrometry and Proteomics Facility, The Netherlands Cancer Institute)

  • Hanne Meijers-Heijboer

    (VU University Medical Center)

  • Hans Joenje

    (VU University Medical Center)

  • Gustavo Glusman

    (Institute for Systems Biology)

  • Jared Roach

    (Institute for Systems Biology)

  • Leroy Hood

    (Institute for Systems Biology)

  • David Galas

    (Luxembourg Centre for Systems Biomedicine, House of Biomedicine
    Pacific Northwest Diabetes Research Institute)

  • Claire Wyman

    (Cancer Genomics Center
    Erasmus Medical Center)

  • Rudi Balling

    (Luxembourg Centre for Systems Biomedicine, House of Biomedicine)

  • Johan den Dunnen

    (Leiden University Medical Center)

  • Johan P. de Winter

    (VU University Medical Center)

  • Roland Kanaar

    (Cancer Genomics Center
    Erasmus Medical Center)

  • Richard Gelinas

    (Institute for Systems Biology)

  • Josephine C. Dorsman

    (VU University Medical Center)

Abstract

Fanconi anaemia (FA) is a hereditary disease featuring hypersensitivity to DNA cross-linker-induced chromosomal instability in association with developmental abnormalities, bone marrow failure and a strong predisposition to cancer. A total of 17 FA disease genes have been reported, all of which act in a recessive mode of inheritance. Here we report on a de novo g.41022153G>A; p.Ala293Thr (NM_002875) missense mutation in one allele of the homologous recombination DNA repair gene RAD51 in an FA-like patient. This heterozygous mutation causes a novel FA subtype, ‘FA-R’, which appears to be the first subtype of FA caused by a dominant-negative mutation. The patient, who features microcephaly and mental retardation, has reached adulthood without the typical bone marrow failure and paediatric cancers. Together with the recent reports on RAD51-associated congenital mirror movement disorders, our results point to an important role for RAD51-mediated homologous recombination in neurodevelopment, in addition to DNA repair and cancer susceptibility.

Suggested Citation

  • Najim Ameziane & Patrick May & Anneke Haitjema & Henri J. van de Vrugt & Sari E. van Rossum-Fikkert & Dejan Ristic & Gareth J. Williams & Jesper Balk & Davy Rockx & Hong Li & Martin A. Rooimans & Anne, 2015. "A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51," Nature Communications, Nature, vol. 6(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9829
    DOI: 10.1038/ncomms9829
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