[Nijmegen breakage syndrome in Slovakia]. / Nijmegen breakage syndrom na slovensku.

BACKGROUND: The autosomal recessive Nijmegen breakage syndrome (NBS) is a DNA repair 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 657de15, 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 5.2 million 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.

[Presence of Y-specific sequences in patients with Turner syndrome as a presymptomatic marker of increased risk of gonadoblastoma]. / Prítomnost Y-specifických sekvencií u pacientok s Turnerovým syndrómom ako presymptomatický marker zvýseného rizika gonadoblastómu.

The risk of the origin of neoplasms in patients with gonadal dysgenesis and the presence of Y chromosome mosaicism has been known for a long period. The majority of hidden mosaicism is however not detectable by means of cytogenetic methods. The authors of this study deal with the detection of Y specific chromosomal sequences in 86 patients with Turner syndrome by means of polymerase chain reaction (PCR) and compare the results of this method with cytogenetic findings. The presence of Y specific sequences was proven in 8 patients (9.3%) which correlates with the results of several recent studies. In two cases, the Y chromosome fragment was verified also cytogenetically, in five patients, the diagnose was made more accurate at an originally non-specified marker, and in two cases, the cytogenetic examination has assessed the finding of X chromosome only. PCR is a more sensitive and a more precise method of the assessment of Y chromosome mosaicism in patients with Turner syndrome enabling more effectively to single out persons under the risk of rudimentary gonads gonadoblastoma development. (Fig. 5, Ref. 32.)

[Thanatophoric nanism and histopathologic bone changes]. / Thanatoforický nanizmus a histopatologické kostné zmeny.

The authors describe in a neonate with thanatophoric nanism histopathological changes of the bones. According to X-ray findings type I was involved, the histopathological changes corresponded to type II according to Langer's classification. The consanguinity of the parents suggested the autosomal recessive type of heredity and the presence of pseudo-diastrophic dysplasia in two grade 1 cousins is considered by the authors as an incidental coincidence. The described case confirms the assumed clinical and genetic heterogeneity of thanatophoric nanism.

[Identification of a de novo mutation in a factor FVIII:C gene in a family requesting prenatal diagnosis of hemophilia A]. / Identifikácia de novo mutácie v géne pre faktor FVIII:C v rodine pozadujúcej prenatálnu diagnostiku hemofílie A.

Hemophilia is caused by wide spectrum of different mutations in the F8C gene which made the direct DNA diagnosis of the diseases not the case of choice. Indirect DNA diagnosis by means of linked restriction fragment length polymorphisms (RFLPs) provides the alternative. Using this method authors identified de novo mutation in a family requiring prenatal diagnosis of hemophilia A. This de novo mutation arose during the spermatogenesis of the proband's father. Attempts to characterize the mutation on the molecular level are presented. (Ref. 15, Fig. 1.).

[Chromosome aberrations in children with the Williams-Beuren syndrome]. / Chromozómové aberácie u detí s Williamsovým-Beurenovým syndrómom.

Karyotypic examinations were carried out in 10 children suffering from Williams-Beuren's syndrome. Chromosomal aberrations were established in two of the children. In one case the mosaic pattern of Klinefelter's syndrome was recorded, evidently presenting an instance of coincidence. In the other case deletion of the long arm of chromosome 6 (q22.2q23) was demonstrated, which according to the authors' hypothesis may represent an alternative localization of the phenotypic traits of Williams-Beuren's syndrome or of its assumed underlying defect, namely derangement of the regulation of calcium metabolism. The value of cytogenetic examination of children with Williams-Beuren's syndrome in elucidating the so far obscure pathogenesis of this disease is being emphasized.

[Genetic linkage of the autosomal dominant form of Charcot-Marie-Tooth amyotrophy and 3 genetic markers on chromosome 1]. / Stúdium genetickej väzby medzi autozómovou dominantnou formou amyotrofie Charcot-Marie-Tooth a tromi genetickými markermi chromozómu c. 1.

In a large pedigree with the autosomal dominant form of Charcot-Marie-Tooth neuropathy type I (CMT 1) segregating in four generations, genetic linkage was studied between this disease and three genetic markers from the centromere region of chromosome 1: Duffy blood group (Fy), salivary and pancreatic isoamylases (AMY 1, AMY 2), and DNA polymorphism at the antithrombin III locus, detected with the probe pAT3c. The lod-scores found do not support linkage between CMT 1 and both Fy and AT 3, since they are negative for all recombination frequencies. Very close linkage could have been excluded. For the AMY polymorphism, the pedigree was not linkage-informative. In agreement with the data from literature, these results support the notion of genetic heterogeneity of CMT 1: in the pedigree under study, the responsible locus is probably not in the centromeric region of the chromosome 1, where it was shown to map to in several other pedigrees. Thus, there seem to exist at least two loci responsible for this type of CMT disease.