Definition
Nijmegen breakage syndrome (NBS) is an autosomal-recessive chromosome instability disorder characterized by growth and developmental defects (growth retardation, severe and progressive microcephaly, a distinct facial appearance, lack of secondary sex characteristics in females, and frequent cryptorchism in males), immunodeficiency, high susceptibility to lymphoid malignancies, hypersensitivity to ionizing radiation, and aberrant cell-cycle checkpoint control (Varon et al. 2017; Seemanova et al. 2016). The disease is caused by mutations in the NBN gene (also abbreviated NBS, NBS1) and is located on chromosome 8q21 (GRCh38.p2: 89,933,336–89,984,733).
Introduction/Background
In 1981, Weemaes et al. from the University Hospital of Nijmegen, the Netherlands, first described the syndrome in two Dutch brothers with microcephaly, short stature, skin pigmentation abnormalities, mental...
This is a preview of subscription content, log in via an institution to check access.
References
Deripapa E, Balashov D, Rodina Y, et al. Prospective study of a cohort of Russian Nijmegen breakage syndrome patients demonstrating predictive value of low kappa deleting recombination excision circle (KREC) numbers and beneficial effect of hematopoietic stem cell transplantation (HSCT). Front Immunol. 2017;8:807.
Gennery AR, Slatter MA, Bhattacharya A, et al. The clinical and biological overlap between Nijmegen breakage syndrome and Fanconi anemia. Clin Immunol. 2004;113(2):214–9.
Gennery AR, Slatter MA, Bhattacharya A, et al. Bone marrow transplantation for Nijmegan breakage syndrome. J Pediatr Hematol Oncol. 2005;27(4):239.
Nakanishi K, Taniguchi T, Ranganathan V, et al. Interaction of FANCD2 and NBS1 in the DNA damage response. Nat Cell Biol. 2002;4(12):913–20.
New HV, Cale CM, Tischkowitz M, et al. Nijmegen breakage syndrome diagnosed as Fanconi anaemia. Pediatr Blood Cancer. 2005;44(5):494–9.
Pastorczak A, Szczepanski T, Mlynarski W. Clinical course and therapeutic implications for lymphoid malignancies in Nijmegen breakage syndrome. Eur J Med Genet. 2016;59(3):126–32.
Resnick IB, Kondratenko I, Togoev O, et al. Nijmegen breakage syndrome: clinical characteristics and mutation analysis in eight unrelated Russian families. J Pediatr. 2002;140(3):355–61.
Seemanova E, Passarge D, Beneskova J, et al. Familial microcephaly with normal intelligence, immunodeficiency, and risk for lymphoreticular malignancies: a new autosomal recessive disorder. Am J Med Genet. 1985;20(4):639–48.
Seemanová E, Sperling K, Neitzel H, et al. Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability. J Med Genet. 2006;43(3):218–24.
Seemanova E, Varon R, Vejvalka J, et al. The Slavic NBN founder mutation: a role for reproductive fitness? PLoS One. 2016;11(12):e0167984.
Slack J, Albert MH, Balashov D, et al. Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders. J Allergy Clin Immunol. 2018;141(1):322–328.e10.
Varon R, Vissinga C, Platzer M, et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell. 1998;93(3):467–76.
Varon R, Seemanova E, Chrzanowska K, et al. Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations. Eur J Hum Genet. 2000;8:900–2.
Varon R, Dutrannoy V, Weikert G, et al. Mild Nijmegen breakage syndrome phenotype due to alternative splicing. Hum Mol Genet. 2006;15(5):679–89.
Varon R, Demuth I, Chrzanowska KH. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2018. 999 May 17 [updated 2017 Feb 2].
Weemaes CM, Hustinx TW, Scheres JM, et al. A new chromosomal instability disorder: the Nijmegen breakage syndrome. Acta Paediatr Scand. 1981; 70(4):557–64.
Wolska-Kuśnierz B, Gregorek H, Chrzanowska K, et al. Nijmegen breakage syndrome: clinical and immunological features, long-term outcome and treatment options – a retrospective analysis. J Clin Immunol. 2015;35(6):538–49.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this entry
Cite this entry
Sharapova, S.O., Kostyuchenko, L.V. (2019). Nijmegen Breakage Syndrome (NBS1). In: MacKay, I., Rose, N. (eds) Encyclopedia of Medical Immunology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9209-2_161-1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-9209-2_161-1
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-9209-2
Online ISBN: 978-1-4614-9209-2
eBook Packages: Springer Reference MedicineReference Module Medicine