Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657de15, in three Slav populations

Nijmegen breakage syndrome (NBS) is a chromosomal instability disorder, cli nically characterised by microcephaly, immunodeficiency, radiosensitivity a nd a very high predisposition to lymphoid malignancy. Recently, it was demo nstrated that mutations in the NBS1 gene are responsible for NBS. Most of t he NBS patients known so far are of Slav origin and carry a major founder m utation 657del5 in exon 6 of the NBS1 gene. In this study we estimated the prevalence of the 657del5 mutation in the Czech Republic, Poland and the Uk raine. We found an unexpectedly high carrier frequency of the 657del5 mutat ion (1/177) in the three Slav populations, a factor that may contribute to cancer frequency in those countries. In addition, we show that NBS patients are often diagnosed late and therefore receive inappropriate therapy.