Abstract
Nijmegen breakage syndrome (NBS) is an autosomal recessive syndrome of chromosomal instability. Clinicalfeatures are prenatal as well as postnatal growth retardation, severe congenital microcephaly, humoral and cellularimmunodeficiency, respiratory infections, predisposition to bronchiectasia, high risk for lymphoreticular malig-nancy.
Characteristic facies with low forehead, prominent midface, retromicrognathia, large auricles is apparentfrom the age of 3 years. Laboratory findings include low immunoglobulins, chromosomal breaks with typicalrearrangement 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 differentmutations were detected so far in NBS1 gene, mutation 657del5 is characteristic for Slavonic populations. Detectionof the NBS1 mutations allows an exact postnatal and prenatal diagnosis.
Nibrin, the protein product of NBS1 geneprotects cell and chromosomes from deleterious effects of ionising radiation. Hyperradiosensitivity of 657del5homozygotes has important implications for clinical prognosis and for treatment after the patients developmalignancy.