Summary:
Nijmegen breakage syndrome (NBS) is an autosomal recessive syndrome of chromosomal instability. Clinical
features are prenatal as well as postnatal growth retardation, severe congenital microcephaly, humoral and cellular
immunodeficiency, respiratory infections, predisposition to bronchiectasia, high risk for lymphoreticular malig-
nancy. Characteristic facies with low forehead, prominent midface, retromicrognathia, large auricles is apparent
from the age of 3 years. Laboratory findings include low immunoglobulins, chromosomal breaks with typical
rearrangement of chromosomes 7 and/or 14 and cellular hyperradiosensitivity and radioresistant DNA synthesis.
The gene, responsible for NBS called NBS1, was localised in 1997 on 8q21 and cloned in 1998. Six different
mutations were detected so far in NBS1 gene, mutation 657del5 is characteristic for Slavonic populations. Detection
of the NBS1 mutations allows an exact postnatal and prenatal diagnosis. Nibrin, the protein product of NBS1 gene
protects cell and chromosomes from deleterious effects of ionising radiation. Hyperradiosensitivity of 657del5
homozygotes has important implications for clinical prognosis and for treatment after the patients develop
malignancy.
Key words:
Nijmegen breakage syndrome, autosomal recessive inheritance, chromosomal instability, hyper-
radiosensitivity, risk of malignancy, NBS1 gene, slavic mutation 657del5, nibrin
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