Nijmegen Breakage Syndrome in Slovakia
Seemanová E., 1Pohanka V., 2Seeman P., 3Mišovicová N., 4Behunová J.,5Kvasnicová M., 5Dlholucký S., 6Valachová A., 7Cisarik F., 8Veghová E., 9Varon R., 9Sperling K.
Oddělení klinické genetiky ÚBLG 2. LF UK a FNM, Praha 1Šrobárův ústav, Dolný Smokovec 2Klinika dětské neurologie 2. LF UK a FNM, Praha3Klinika dětí a dorastu JLF UK, Martin 4Klinika dětí a dorastu UPJŠ, Košice 5Nemocnice s poliklinikou, Banská Bystrica 6Nemocnice s poliklinikou, Trenčín 7Nemocnice s poliklinikou, Žilina 8Fakultní nemocnice s poliklinikou, Bratislava 9Institut für Humangenetik der Humboldt Universität Berlin, Německo
Backround. The autosomal recessive Nijmegen breakage syndrome (NBS) is aDNArepair disorder due to a mutation
in the NBS1 gene on 8q21. Hyperradiosensitivity and high risk for lymphoreticular malignancy are important reasons
for early diagnosis and prevention by avoidance of ionisation. The frequency of NBS heterozygotes of the mutation
657del5, which is predominant in the Slavic population was estimated to be in the range of 1:90-1:314 in different
parts 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 explained
to be due to underdiagnosing because the rate of prenatal lethality in the NBS families is not increased or it is even
lower 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 primary
and 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 among
the 11 newly recognized patients has been achieved in the previous 4 years. The occurrence of homozygotes was
relatively higher in Slovakia with 5 million inhabitants (14 patients in 11 families) than in the Czech Republic with
a population of 10 million (21 patients in 14 families), and therefore the frequency of NBS heterozygotes was studied
among 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 to
traditional subisolates the population is not in the genetic equilibrium. It explains the high prevalence of alcaptonuria
in Slovakia in the middle of last century, which is a rare disorder in other countries.
Nijmegen breakage syndrome (NBS), NBS1 gene, 657del5 and R215W mutations, prevalence of NBS
homozygotes, frequency of NBS carriers in Slovak population, high proportion of endogamic marriages in Slovakia.