Nijmegen breakage syndrom na Slovensku

Nijmegen Breakage Syndrome in Slovakia

Backround.
The autosomal recessive Nijmegen breakage syndrome (NBS) is aDNArepair disorder due to a mutationin the NBS1 gene on 8q21. Hyperradiosensitivity and high risk for lymphoreticular malignancy are important reasonsfor early diagnosis and prevention by avoidance of ionisation. The frequency of NBS heterozygotes of the mutation657del5, which is predominant in the Slavic population was estimated to be in the range of 1:90-1:314 in differentparts of Poland, and 1:128-154 among Czech newborns, born 20 years ago.Methods and Results. Lower prevalence of affected homozygotes born in Czechoslovakia in the period 1969- 1992(24 among 5.2million newborns corresponds to 1:271000) than expected on the basis of carrier frequency is explainedto be due to underdiagnosing because the rate of prenatal lethality in the NBS families is not increased or it is evenlower than in the general population. The underdiagnosing of NBS is emphasized also by the mean age at diagnosis(7,5 years) although severe microcephaly is present at birth. The possibility to offer effective prevention of primaryand secondary malignancies becomes the motivation for interdisciplinary collaboration with paediatricians, neurologists,immunologists and clinical geneticists. A decrease of the mean age down to 6 months at diagnosis amongthe 11 newly recognized patients has been achieved in the previous 4 years. The occurrence of homozygotes wasrelatively higher in Slovakia with 5 million inhabitants (14 patients in 11 families) than in the Czech Republic witha population of 10 million (21 patients in 14 families), and therefore the frequency of NBS heterozygotes was studiedamong 2996 newborns born in 2002-2003 in 12 maternity hospitals of west, middle and east Slovakia. Surprisingly,only 3 heterozygotes were found.Conclusions. This discrepancy of heterozygote frequency and the number of homozygotes shows that due totraditional subisolates the population is not in the genetic equilibrium. It explains the high prevalence of alcaptonuriain Slovakia in the middle of last century, which is a rare disorder in other countries.

Key words:
Nijmegen breakage syndrome (NBS), NBS1 gene, 657del5 and R215W mutations, prevalence of NBShomozygotes, frequency of NBS carriers in Slovak population, high proportion of endogamic marriages in Slovakia.