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The Fanconi anaemia group G gene FANCG is identical with XRCC9

Nature Genetics volume 20, pages 281–283 (1998)Cite this article

Abstract

Fanconi anemia (FA) is an autosomal recessive disease with diverse clinical symptoms including developmental anomalies, bone marrow failure and early occurrence of malignancies1. In addition to spontaneous chromosome instability, FA cells exhibit cell cycle disturbances and hypersensitivity to cross-linking agents1. Eight complementation groups (A-H) have been distinguished2, each group possibly representing a distinct FA gene3. The genes mutated in patients of complementation groups A (FANCA; Refs 4,5) and C (FANCC; ref. 6) have been identified, and FANCD has been mapped to chromosome band 3p22-26 (ref. 7). An additional FA gene has recently been mapped to chromosome 9p (ref. 8). Here we report the identification of the gene mutated in group G, FANCG, on the basis of complementation of an FA-G cell line and the presence of pathogenic mutations in four FA-G patients. We identified the gene as human XRCC9, a gene which has been shown to complement the MMC-sensitive Chinese hamster mutant UV40, and is suspected to be involved in DNA post-replication repair or cell cycle checkpoint control9,10. The gene is localized to chromosome band 9p13 (ref. 9), corresponding with a known localization of an FA gene.

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Figure 1: Complementation of cross-linker hypersensitivity by pFAG9.
Figure 2: The 5' UTR of FANCG cDNA inserts recovered from transfected MMC-resistant EUFA143.
Figure 3: Family FA15BER and detection of the IVS13-1G→C mutation in FANCG.
Figure 4: FANCG mRNA expression.

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Acknowledgements

We thank R. Dietrich and the FA families who participated in this research project, without whose cooperation this study would have been impossible. We are grateful to B. Schmalenberger, W. Ebell, U. Schulte-Overberg-Schmidt and U. Glöckel for referring patients. We also thank J. Steltenpool and L. van der Weel for technical assistance. This project was supported by the Dutch Cancer Society (project VU-97-1565), the Fanconi Anemia Research Fund Inc., the Commission of the European Union (EUFAR contract PL931562), the National Institutes of Health (HL50131), the Medical Research Council of Canada (MRC) and the Fritz-Thyssen-Stiftung (1997/2061).

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  1. Johan P. de Winter and Quinten Waisfisz: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Human Genetics, Free University, Van der Boechorststraat 7, Amsterdam, NL-1081 BT, The Netherlands

    Johan P. de Winter, Quinten Waisfisz, Martin A. Rooimans, Carola G.M. van Berkel, Jan C. Pronk, Fré Arwert & Hans Joenje

  2. Program in Genetics and Genomic Biology, Research Institute, The Hospital for Sick Children, 555 University Avenue

    Lucine Bosnoyan-Collins, Noa Alon, Madeleine Carreau & Manuel Buchwald

  3. Department of Molecular and Medical Genetics, The University of Toronto, Toronto, Ontario, Canada

    Lucine Bosnoyan-Collins, Noa Alon, Madeleine Carreau & Manuel Buchwald

  4. Institut für Humangenetik, Charité-Campus Virchow-Klinikum, Humboldt Universität Berlin, Augustenburger Platz 1, Berlin, D-13353, Germany

    Olaf Bender, Ilja Demuth & Martin Digweed

  5. Institut für Humangenetik, Universität Würzburg, Biozentrum Am Hubland, Würzburg, D-8700, Germany

    Detlev Schindler & Holger Hoehn

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Correspondence to Hans Joenje.

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de Winter, J., Waisfisz, Q., Rooimans, M. et al. The Fanconi anaemia group G gene FANCG is identical with XRCC9. Nat Genet 20, 281–283 (1998). https://doi.org/10.1038/3093

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