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Nijmegen Breakage Syndrome

  • Conference paper
Immune-Mediated Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 601))

Abstract

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, characterized by microcephaly, growth retardation, immunodeficiency, chromosome instability, radiation sensitivity, and a strong predisposition to lymphoid malignancy. The gene responsible for the development of this syndrome (NBS1) was mapped on chromosome 8q21. The product of this gene—nibrin—is a protein with 95 kDa molecular weight (p95). The same mutation in the NBS1 gene (deletion 657del5) was detected in most of the evaluated patients. In this chapter, we describe the analysis of the literature and our results on clinical and immunological features and genetic evaluation of 21 NBS patients.

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References

  • Carney, J.P., Maser, R.S., Olivares, H., Davis, E.M., Le Beau, M., Yates, J.R., 3rd, Hays, L., Morgan, W.F. and Petrini, J.H. (1998) The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93, 477–486.

    Article  PubMed  CAS  Google Scholar 

  • Cerosaletti, K.M., Lange, E., Stringham, H.M., Weemaes, C.M., Smeets, D., Solder, B., Belohradsky, B.H., Taylor, A.M., Karnes, P., Elliott, A., Komatsu, K., Gatti, R.A., Boehnke, M. and Concannon, P. (1998) Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a common founder haplotype. Am. J. Hum. Genet. 63, 125–134.

    Article  PubMed  CAS  Google Scholar 

  • Chrzanowska, K.H. (1996) Microcephaly with chromosomal instability and immunodeficiency–Nijmegen syndrome. Pediatr. Pol. 71, 223–234.

    PubMed  CAS  Google Scholar 

  • Chrzanowska, K.H., Bekiesinska-Figatowska, M. and Jozwiak, S. (2002) Corpus callosum hypoplasia and associated brain anomalies in Nijmegen breakage syndrome. J. Med. Genet. 39, E25.

    Article  PubMed  CAS  Google Scholar 

  • Chrzanowska, K.H., Kleijer, W.J., Krajewska-Walasek, M., Bialecka, M., Gutkowska, A., Goryluk-Kozakiewicz, B., Michalkiewicz, J., Stachowski, J., Gregorek, H., Lyson-Wojciechowska, G., et al. (1995) Eleven Polish patients with microcephaly, immunodeficiency, and chromosomal instability: the Nijmegen breakage syndrome. Am. J. Med. Genet. 57, 462–471.

    Article  PubMed  CAS  Google Scholar 

  • D’Amours, D. and Jackson, S.P. (2002) The Mre11 complex: at the crossroads of DNA repair and checkpoint signalling. Nat. Rev. Mol. Cell. Biol. 3, 317–327.

    Article  PubMed  CAS  Google Scholar 

  • Digweed, M. and Sperling, K. (2004) Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks. DNA Repair (Amst) 3, 1207–1217.

    Article  CAS  Google Scholar 

  • Elledge, S. (1996) Cell cycle checkpoints: preventing identity crisis. Science 274, 1664–1672.

    Article  PubMed  CAS  Google Scholar 

  • Featherstone, C. and Jackson, S.P. (1998) DNA repair: the Nijmegen breakage syndrome protein. Curr. Biol. 8, R622–R625.

    Article  PubMed  CAS  Google Scholar 

  • Gatei, M., Young, D., Cerosaletti, K.M., Desai-Mehta, A., Spring, K., Kozlov, S., Lavin, M.F., Gatti, R.A., Concannon, P. and Khanna, K. (2000) ATM-dependent phosphorylation of nibrin in response to radiation exposure. Nat. Genet. 25, 115–119.

    Article  PubMed  CAS  Google Scholar 

  • Green, A.J., Yates, J.R., Taylor, A.M., Biggs, P., McGuire, G.M., McConville, C.M., Billing, C.J. and Barnes, N.D. (1995) Severe microcephaly with normal intellectual development: the Nijmegen breakage syndrome. Arch. Dis. Child. 73, 431–434.

    Article  PubMed  CAS  Google Scholar 

  • Howlett, N.G., Scuric, Z., D’Andrea, A.D. and Schiestl, R.H. (2006) Impaired DNA double strand break repair in cells from Nijmegen breakage syndrome patients. DNA Repair (Amst) 5, 251–257.

    Article  CAS  Google Scholar 

  • Kastan, M.B. and Lim, D.S. (2000) The many substrates and functions of ATM. Nat. Rev. Mol. Cell. Biol. 1, 179–186.

    Article  PubMed  CAS  Google Scholar 

  • Kastan, M.B., Lim, D.S., Kim, S.T., Xu, B. and Canman, C. (2000) Multiple signaling pathways involving ATM. Cold Spring Harb. Symp. Quant. Biol. 65, 521–526.

    Article  PubMed  CAS  Google Scholar 

  • Lim, D.S., Kim, S.T., Xu, B., Maser, R.S., Lin, J., Petrini, J.H. and Kastan, M.B. (2000) ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature 404, 613–617.

    Article  PubMed  CAS  Google Scholar 

  • Matsuura, S., Weemaes, C., Smeets, D., Takami, H., Kondo, N., Sakamoto, S., Yano, N., Nakamura, A., Tauchi, H., Endo, S., Oshimura, M. and Komatsu, K. (1997) Genetic mapping using microcell-mediated chromosome transfer suggests a locus for Nijmegen breakage syndrome at chromosome 8q21-24. Am. J. Hum. Genet. 60, 1487–1494.

    Article  PubMed  CAS  Google Scholar 

  • Meyer, S., Kingston, H., Taylor, A.M., Byrd, P., Last, J., Brennan, B., Trueman, S., Kelsey, A., Taylor, G. and Eden, O. (2004) Rhabdomyosarcoma in Nijmegen breakage syndrome: strong association with perianal primary site. Cancer Genet. Cytogenet. 154, 169–174.

    Article  PubMed  CAS  Google Scholar 

  • Michalkiewicz, J., Barth, C., Chrzanowska, K., Gregorek, H., Syczewska, M., Weemaes, C.M., Madalinski, K. and Stachowski, J. (2003) Abnormalities in T and NK lymphocyte phenotype in patients with Nijmegen breakage syndrome. Clin. Exp. Immunol. 134, 482–490.

    Article  PubMed  CAS  Google Scholar 

  • Mirzoeva, O.K. and Petrini, J.H. (2001) DNA damage-dependent nuclear dynamics of the Mre11 complex. Mol. Cell. Biol. 21, 281–288.

    Article  PubMed  CAS  Google Scholar 

  • New, H.V., Cale, C.M., Tischkowitz, M., Jones, A., Telfer, P., Veys, P., D’Andrea, A., Mathew, C.G. and Hann, I. (2005) Nijmegen breakage syndrome diagnosed as Fanconi anaemia. Pediatr. Blood Cancer 44, 494–499.

    Article  PubMed  Google Scholar 

  • Niehues, T., Schellong, G., Dorffel, W., Bucsky, P., Mann, G., Korholz, D. and Gobel, U. (2003) Immunodeficiency and Hodgkin’s disease: treatment and outcome in the DAL HD78-90 and GPOH HD95 studies. Klin. Padiatr. 215, 315–320.

    Article  PubMed  CAS  Google Scholar 

  • Pasic, S. (2002) Aplastic anemia in Nijmegen breakage syndrome. J. Pediatr. 141, 742.

    PubMed  Google Scholar 

  • Petrini, J.H. (1999) The mammalian Mre11-Rad50-nbs1 protein complex: integration of functions in the cellular DNA-damage response. Am. J. Hum. Genet. 64, 1264–1269.

    Article  PubMed  CAS  Google Scholar 

  • Resnick, I.B., Kondratenko, I., Pashanov, E., Maschan, A.A., Karachunsky, A., Togoev, O., Timakov, A., Polyakov, A., Tverskaya, S., Evgrafov, O. and Roumiantsev, A.G. (2003) 657del5 mutation in the gene for Nijmegen breakage syndrome (NBS1) in a cohort of Russian children with lymphoid tissue malignancies and controls. Am. J. Med. Genet. A. 120, 174–179.

    Article  Google Scholar 

  • Resnick, I.B., Kondratenko, I., Togoev, O., Vasserman, N., Shagina, I., Evgrafov, O., Tverskaya, S., Cerosaletti, K.M., Gatti, R.A. and Concannon, P. (2002) Nijmegen breakage syndrome: clinical characteristics and mutation analysis in eight unrelated Russian families. J. Pediatr. 140, 355–361.

    Article  PubMed  Google Scholar 

  • Rosenzweig, S.D., Russo, R.A., Gallego, M. and Zelazko, M. (2001) Juvenile rheumatoid arthritis-like polyarthritis in Nijmegen breakage syndrome. J. Rheumatol 28, 2548–2550.

    PubMed  CAS  Google Scholar 

  • Savitsky, K., Sfez, S., Tagle, D.A., Ziv, Y., Sartiel, A., Collins, F.S., Shiloh, Y. and Rotman, G. (1995) The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species. Hum. Mol. Genet. 4, 2025–2032.

    Article  PubMed  CAS  Google Scholar 

  • Seidemann, K., Henze, G., Beck, J.D., Sauerbrey, A., Kuhl, J., Mann, G. and Reiter, A. (2000) Non-Hodgkin’s lymphoma in pediatric patients with chromosomal breakage syndromes (AT and NBS): experience from the BFM trials. Ann. Oncol. 11 (Suppl 1), 141–145.

    Article  PubMed  Google Scholar 

  • Steffen, J., Maneva, G., Poplawska, L., Varon, R., Mioduszewska, O. and Sperling, K. (2006) Increased risk of gastrointestinal lymphoma in carriers of the 657del5 NBS1 gene mutation. Int. J. Cancer 119, 2970–2973.

    Article  PubMed  CAS  Google Scholar 

  • Taalman, R.D., Hustinx, T.W., Weemaes, C.M., Seemanova, E., Schmidt, A., Passarge, E. and Scheres, J.M. (1989) Further delineation of the Nijmegen breakage syndrome. Am. J. Med. Genet. 32, 425–431.

    Article  PubMed  CAS  Google Scholar 

  • Taalman, R.D., Jaspers, N.G., Scheres, J.M., de Wit, J. and Hustinx, T.W. (1983) Hypersensitivity to ionizing radiation, in vitro, in a new chromosomal breakage disorder, the Nijmegen Breakage Syndrome. Mutat. Res. 112, 23–32.

    PubMed  CAS  Google Scholar 

  • The International Nijmegen Breakage Syndrome Study Group (2000) Nijmegen breakage syndrome. Arch. Dis. Child. 82, 400–406.

    Article  Google Scholar 

  • van der Burgt, I., Chrzanowska, K.H., Smeets, D. and Weemaes, C. (1996) Nijmegen breakage syndrome. J. Med. Genet. 33, 153–156.

    Article  PubMed  Google Scholar 

  • Varon, R., Vissinga, C., Platzer, M., Cerosaletti, K.M., Chrzanowska, K.H., Saar, K., Beckmann, G., Seemanova, E., Cooper, P.R., Nowak, N.J., Stumm, M., Weemaes, C.M., Gatti, R.A., Wilson, R.K., Digweed, M., Rosenthal, A., Sperling, K., Concannon, P. and Reis, A. (1998) Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93, 467–476.

    Article  PubMed  CAS  Google Scholar 

  • Weemaes, C.M., Hustinx, T.W., Scheres, J.M., van Munster, P.J., Bakkeren, J.A. and Taalman, R.D. (1981) A new chromosomal instability disorder: the Nijmegen breakage syndrome. Acta Paediatr. Scand. 70, 557–564.

    Article  PubMed  CAS  Google Scholar 

  • Weemaes, C.M., Smeets, D.F., Horstink, M., Haraldsson, A. and Bakkeren, J.A. (1993) Variants of Nijmegen breakage syndrome and ataxia telangiectasia. Immunodeficiency 4, 109–111.

    PubMed  CAS  Google Scholar 

  • Weemaes, C.M., Smeets, D.F. and van der Burgt, C.J. (1994) Nijmegen Breakage syndrome: a progress report. Int. J. Radiat. Biol. 66, S185–S188.

    Article  PubMed  CAS  Google Scholar 

  • Weemaes, C.M., The, T.H., van Munster, P.J. and Bakkeren, J.A. (1984) Antibody responses in vivo in chromosome instability syndromes with immunodeficiency. Clin. Exp. Immunol. 57, 529–534.

    PubMed  CAS  Google Scholar 

  • Wu, X., Ranganathan, V., Weisman, D.S., Heine, W.F., Ciccone, D.N., O’Neill, T.B., Crick, K.E., Pierce, K.A., Lane, W.S., Rathbun, G., Livingston, D.M. and Weaver, D.T. (2000) ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Nature 405, 477–482.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, B.B. and Elledge, S.J. (2000) The DNA damage response: putting checkpoints in perspective. Nature 408, 433–439.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Russian Clinical Children’s Hospital and Institute for Clinical Genetics, Moscow, Russia

    Irina Kondratenko, Olga Paschenko, Alexandr Polyakov & Andrey Bologov

Authors
  1. Irina Kondratenko
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  2. Olga Paschenko
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  3. Alexandr Polyakov
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  4. Andrey Bologov
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Corresponding author

Correspondence to Irina Kondratenko .

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Editors and Affiliations

  1. Division of Clinical Immunopathology, 5725 Children’s Hospital of Pittsburgh, Main Tower, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Michael R. Shurin (Associate Professor of Pathology and Immunology, Associate Director) (Associate Professor of Pathology and Immunology, Associate Director)

  2. Institute for Continuing Medical Education, Russian Association of Pediatric Allergology and Immunology, Clinical and Research Center of Allergy and Immunology, Ostrovitianova St., Bldg. 6, Moscow, 117513, Russia

    Yuri S. Smolkin (Professor of Immunology, Vise-President, Director) (Professor of Immunology, Vise-President, Director)

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Kondratenko, I., Paschenko, O., Polyakov, A., Bologov, A. (2007). Nijmegen Breakage Syndrome. In: Shurin, M.R., Smolkin, Y.S. (eds) Immune-Mediated Diseases. Advances in Experimental Medicine and Biology, vol 601. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72005-0_6

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