Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9 (original) (raw)

European Journal of Human Genetics volume 8, pages 861–868 (2000)Cite this article

Abstract

FANCG was the third Faconi anaemia gene identified and proved to be identical to the previously cloned XRCC9 gene. We present the pathogenic mutations and sequence variants we have so far identified in a panel of FA-G patients. Mutation screening was performed by PCR, single strand conformational polymorphism analysis and protein truncation tests. Altogether 18 mutations have been determined in 20 families – 97% of all expected mutant alleles. All mutation types have been found, with the exception of large deletions, the large majority is predicted to lead to shortened proteins. One stop codon mutation, E105X, has been found in several German patients and this founder mutation accounts for 44% of the mutant FANCG alleles in German FA-G patients. Comparison of clinical phenotypes shows that patients homozygous for this mutation have an earlier onset of the haematological disorder than most other FA-G patients. The mouse Fancg sequence was established in order to evaluate missense mutations. A putative missense mutation, L71P, in a possible leucine zipper motif may affect FANCG binding of FANCA and seems to be associated with a milder clinical phenotype.

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Authors and Affiliations

  1. Institute of Human Genetics, Charité, Campus Virchow, Humboldt University, Berlin, Germany
    Ilja Demuth, Marcin Wlodarski, Jürgen Kunze, Karl Sperling & Martin Digweed
  2. Division of Medical and Molecular Genetics, Guy's, King's and St Thomas' School of Medicine, London, UK
    Alex J Tipping, Neil V Morgan & Christopher G Mathew
  3. Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam, The Netherlands
    Johan P de Winter & Hans Joenje
  4. Institute of Human Genetics, University of Würzburg, Germany
    Michaela Thiel, Sonja Gräsl & Detlev Schindler
  5. Department of Pediatric Oncology, Dana-Faber Cancer Institute, Boston, USA
    Alan D D'Andrea
  6. Department of Pediatrics, Hematology Unit, Hacettepe University, Ankara
    Cigdem Altay
  7. Institute of Child Health, Istanbul, Turkey
    Hülya Kayserili
  8. Servizio di Citogenetica, Ospetale Elena d'Aosta, Napoli, Italy
    Adriana Zatterale
  9. Children's Hospital, Charité, Campus Virchow, Humboldt University, Berlin, Germany
    Wolfram Ebell

Authors

  1. Ilja Demuth
  2. Marcin Wlodarski
  3. Alex J Tipping
  4. Neil V Morgan
  5. Johan P de Winter
  6. Michaela Thiel
  7. Sonja Gräsl
  8. Detlev Schindler
  9. Alan D D'Andrea
  10. Cigdem Altay
  11. Hülya Kayserili
  12. Adriana Zatterale
  13. Jürgen Kunze
  14. Wolfram Ebell
  15. Christopher G Mathew
  16. Hans Joenje
  17. Karl Sperling
  18. Martin Digweed

Corresponding author

Correspondence toMartin Digweed.

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Demuth, I., Wlodarski, M., Tipping, A. et al. Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9.Eur J Hum Genet 8, 861–868 (2000). https://doi.org/10.1038/sj.ejhg.5200552

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