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Positional cloning of the gene for Nijmegen breakage syndrome

Nature Genetics volume 19, pages 179–181 (1998)Cite this article

Abstract

Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia (AT) variant, is an autosomal recessive disorder characterized by microcephaly, growth retardation, severe combined immunodeficiency and a high incidence of lymphoid cancers. Cells from NBS patients display chromosome instability, hypersensitivity to ionizing radiation and abnormal cell-cycle regulation after irradiation, all of which are characteristics shared with AT. Recently, the NBS locus was mapped at 8q21 by two independent approaches, complementation studies1 and linkage analysis2. Here, we report the positional cloning of the NBS gene, NBS1, from an 800-kb candidate region. The gene comprises 50 kb and encodes a protein of 754 amino acids. The amino-terminal region of the protein shows weak homology to the yeast XRS2, MEK1, CDS1 and SPK1 proteins. The gene is expressed at high levels in the testes, suggesting that it might be involved in meiotic recombination. We detected the same 5-bp deletion in 13 individuals, and conclude that it is likely to be a founder mutation.

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Figure 1: Genomic organization of the NBS1 gene.
Figure 2: A founder mutation in NBS patients.
Figure 3: NBS1 expression.
Figure 4: Amino-acid alignment of the predicted NBS1 protein sequence with the XRS2, MEK1, CDS1 and SPK1 proteins.

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Acknowledgements

The authors would like to thank C. Weemaes, K. Sperling, K.H. Chrzanowska, the patients and their families for collection of NBS samples, H. Nanba for collection of control samples, and N. Niikawa, Y. Jinno, H. Tomita, Y. Furuichi, J. Nakura, T. Kajii and K. Miyagawa for helpful discussions. The authors also thank T. Jo, S. Kunisada, M. Ueda, A. Kodama, K. Takeuchi, Y. Yamane and M. Kobayashi for laboratory assistance. This work was supported by the Ministry of Education, Science and Culture of Japan.

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Authors and Affiliations

  1. Department of Radiation Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima , Japan

    Shinya Matsuura, Hiroshi Tauchi, Asako Nakamura, Noriko Kondo, Shuichi Sakamoto, Satoru Endo & Kenshi Komatsu

  2. University Hospital of Nijmegen, Nijmegen , The Netherlands

    Dominique Smeets

  3. Dr. von Haunersches Kinderspital, München, Germany

    Brigitte Solder & Bernd H. Belohradsky

  4. Montreal Children's Hospital, Montreal, Canada

    Vazken M. Der Kaloustian

  5. Department of Molecular and Cell Genetics, School of Life Science, Tottori University, Tottori, Japan

    Mitsuo Oshimura

  6. Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Japan

    Minoru Isomura & Yusuke Nakamura

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  1. Shinya Matsuura
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Correspondence to Kenshi Komatsu.

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Matsuura, S., Tauchi, H., Nakamura, A. et al. Positional cloning of the gene for Nijmegen breakage syndrome. Nat Genet 19, 179–181 (1998). https://doi.org/10.1038/549

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