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FB2026_03
,
released September 17, 2026
This report describes Nijmegen breakage syndrome, which shows autosomal recessive inheritance. The human gene implicated in this disease is NBN (also known as NBS1), a DNA repair protein that is also associated with aplastic anemia (MIM:609135) and acute lymphoblastic leukemia (MIM:613065). There is a single high-ranking ortholog of NBN in Drosophila, nbs. Several alleles have been generated for nbs, including amorphs and hypomorphs, RNAi targeting constructs, and other alleles generated by insertional mutagenesis.
The human gene NBN has not been introduced into flies.
Homozygous nbs hypomorphs have an increased rate of double-stranded DNA breaks and telomeric fusions. In nbs mutants, over-expression of Su(var)205 (the Drosophila ortholog of the heterochromatin maintenance protein HP1) can decrease the frequency of double-stranded breaks.
[updated Jan 2020 by FlyBase; FBrf0222196]
[NIJMEGEN BREAKAGE SYNDROME; NBS](https://omim.org/entry/251260)
[NIBRIN; NBN](https://omim.org/entry/602667)
The principal clinical manifestations of Nijmegen breakage syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin) and radiosensitivity are other integral manifestations of the syndrome. (Chrzanowska et al. 2012, pubmed:22373003.)
Nijmegen breakage syndrome and the phenotypically indistinguishable Berlin breakage syndrome are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer. [from MIM:251260, 2020.01.24]
The first NBS patients were described in Nijmegen in 1981 by Weemaes et al. (pubmed:7315300) and the genetic background of this disease was discovered by Varon et al. 1998 (pubmed:9590180) and Gorski et al. 2003 (pubmed:12845677). They cloned a gene encoding a novel protein, nibrin (NBN gene), containing two modules found in cell cycle checkpoint proteins, a forkhead-associated domain adjacent to a breast cancer carboxy-terminal domain. A truncating 5 bp deletion (c.657_661del5, pK219fsX19) was identified in the majority of NBS patients. In the original report, more than 200 NBS cases were described, the majority among Slavic populations and with a founder mutation in the NBN gene (c.657_661del5). The prevalence of this mutation in the Slavic countries (Poland, Ukraine, Czech Republic) was subsequently analyzed, revealing unexpectedly high (1/177) carrier frequency of the founder mutation (Varon et al. 2000, pubmed:11093281). (Adapted from Pastorczak et al. 2016 and references therein, pubmed:26826318.)
Ataxia-telangiectasia variant-1 is the designation applied to the Nijmegen breakage syndrome and AT variant-2 is the designation for the Berlin breakage syndrome, which differ only in complementation studies. [from MIM:251260, 2020.01.24]
Patients with AT variant-1 are clinically indistinguishable from those with AT variant-2. These patients share mitogenic features with AT, such as spontaneous chromosomal instability, clonal occurrence of rearrangements involving, in particular, chromosomes 7 and 14, chromosomal and cellular hypersensitivity to irradiation, and radioresistant DNA synthesis. (Wegner et al. 1998 pubmed:3277755; Saar et al 1997 pubmed:9042920.) [from MIM:251260, 2020.01.24]
The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. (Chrzanowska et al. 2012, pubmed:22373003.)
One to one: 1 human gene to 1 Drosophila gene.
Single, high-ranking ortholog of human NBN.