Rolf-Dieter Wegner

The 11q;22q translocation: A collaborative study of 20 new cases and analysis of 110 families

SummaryFollowing a previous collaborative study (Fraccaro et al. 1980), 20 new cases of 11q;22q translocation are described. Twelve families were ascertained through an unbalanced carrier of the translocation and eight cases were ascertained as balanced carriers. A segregation analysis was performed on the 110 families so far published. It was concluded that the 11q;22q translocation is a relatively frequent event, and that all the cases thus far reported might have the same breakpoints at 11q23.3 and 22q11.2. The translocation seems to be independent of environmental factors and it seems to have a low rate of mutation as indicated by the scarcity of de novo cases. The new data confirmed that only one type of unbalanced karyotype (47,XX or XY+der(22)t(11;22)(q23.3;q11.2)) is found among the offspring of the translocation carriers. The minimal overall recurrence risk for an unbalanced translocation was estimated to 2%. There was no difference between the recurrence risks for male and female balanced carriers, while the trend was confirmed of an excess of female balanced carriers among the phenotypically normal offspring of the t(11;22) female carriers.

Frequency and distribution of sister-chromatid exchanges in a case of Fanconi's anemia.

SummaryIn lymphocytes of a 7-year-old boy with Fanconis anemia the frequencies and sites of sister-chromatid exchanges (SCE) were studied with the BrdU-Giemsa method. The average frequency of SCE (8.8 per metaphase) and the inter-and intrachromosomal distribution of SCE was not significantly different from the controls.ZusammenfassungMit Hilfe der BrdU-Giemsa-Technik wurden die Häufigkeit und Verteilung von Schwesterstrangaustausch bei einem 7 Jahre alten Jungen mit Fanconi-Anämie bestimmt. Die durchschnittliche Häufigkeit von Schwesterstrangaustauschen (8,8 pro Metaphase) und die inter-und intrachromosomale Verteilung der Schwesterstrangaustausche zeigten keinen Unterschied zu Kontrollen.

AT-related disorder

Two sisters with a complex clinical pattern, including microcephaly, microgenia, defects of skin pigmentation, anal stenosis/atresia, and combined immunodeficiency together with spontaneous chromosomal instability and cellular hypersensitivity to X‐rays and bleomycin are described. Complementation studies on heterokaryons proved that the underlying genetic defect is non‐allelic with that of patients with ataxia telangiectasia (complementation groups AB‐E) and the Nijmegen breakage syndrome, but identical with the case described by Conley et al. (1986).

DNA, FISH and complementation studies in ICF syndrome : DNA hypomethylation of repetitive and single copy loci and evidence for a trans acting factor

ICF syndrome (ICFS) is a rare immunodeficiency disorder characterized by instability of the pericentromeric heterochromatin predominantly of chromosomes 1 and 16. DNA methylation studies in two unrelated ICFS patients provide further evidence for a marked hypomethylation of satellite 2 DNA. The ICFS-specific disturbances of chromatin structure take place within the satellite 2 DNA regions, as demonstrated by fluorescence in situ hybridization analysis. Moreover, methylation studies of genomic imprinted loci D15S63, D15S9, and H19 have revealed hypomethylation to different degrees in both patients; this provides evidence for hypomethylation at autosomal single copy loci in ICFS. Cell fusion experiments have revealed a distinct reduction of chromosomal abnormalities in ICFS cells after fusion with normal cells, suggesting that the abnormalities are caused by the loss of function of an as yet unknown trans acting factor. Although it is now clear that wide-spread DNA hypomethylation is a characteristic feature of ICFS, neither the cause and mechanism of hypomethylation nor their relationship to the clinical symptoms is known. We speculate that a phenotypic effect might result from tissue-dependent abnormal gene expression and/or from a possible structural disturbance of DNA domains, which, with respect to the immunodeficiency, partially prevents the normal somatic recombinations in immunologically active cells.

Has diagnostic ultrasound mutagenic effects

SummaryChinese hamster ovary cells were treated with ultrasound from a fetal pulse detector (Eucotone, Siemens) operated at 10 mW/cm2 and 2.2 MHz. The frequencies of structural chromosomal aberrations and of sister chromatid exchanges were not increased by the treatment. There was no indication of single-strand breaks induced by ultrasound in the G2 phase of the cell cycle.

Characterisation of a Xp21 microdeletion syndrome in a 2-year-old boy with muscular dystrophy, glycerol kinase deficiency and adrenal hypoplasia congenita.

SummaryWe report a 2-year-old boy with Duchenne muscular dystrophy (DMD), glycerol kinase deficiency (GK) and adrenal hypoplasia congenita (AHC). At three weeks of age, the patient was hospitalized for the first time with symptoms of hypotone dehydration because of AHC, At present, he shows severe muscular hypotonia and developmental delay. The patient and his family were referred to us for prenatal diagnosis and carrier testing in the mother of the patient and the mothers sister, respectively. The patients DNA was examined by Southern blot and polymerase chain reaction analyses, using cDNA and genomic probes within and around the dystrophin (DYS) locus. A deletion was revealed, spanning DXS28, the whole dystrophin locus, DXS84 and DXS148, whereas DXS67, DXS68 (pter) and OTC (cen) were found to be retained. The cytogenetically visible microdeletion was also seen in the patients mother, but not in the mothers sister or the patients maternal grandmother. Our findings support the locus order pter-DXS67-DXS68-DXS28-AHC-GK-DMD-cen.

Expression of fra(X)(q28) is Suppressed in man-mouse hybrid cells

SummaryThe fate of fra(X) was followed after fusion of cells donated by a male fra(X) carrier with mouse A9 cells. Suppression of the fragile site was found in the hybrids as well as in human cells co-cultivated with mouse cells.

Ring Y chromosome: cytogenetic and molecular characterization

A female patient with Turner syndrome and the karyotype mos45,X/46,X,r(Y)/46,XY is described. Physical mapping of the ring chromosome by Y‐specific single‐copy and moderately repeated DNA sequences as molecular probes showed that, in addition to the heterochromatic part of Yq, a considerable portion of the Yp has also been lost in the course of the rearrangement. Thus, molecular findings provide independent support that this structurally abnormal sex chromosome is a ring Y and agree with the generally accepted model of ring formation requiring breaks in both chromosome arms. Clinical consequences of Y chromosome mosaicism in patients with Turner syndrome are discussed.

Does Pulsed-Doppler Ultrasound Have Mutagenic Effects? Application of the Ames Mutagenicity Assay to Test Pulsed-Doppler Equipment

Measurement of fetal blood flow has been accepted using pulsed‐Doppler ultrasound. Until recently, there has been a lack of investigations concerning the potential risks of this method. The possible mutagenic effect of a pulsed‐Doppler system was examined in vitro by applying the Ames test. Tester strains of Salmonella typhimurium indicating point mutations were irradiated (TA 98, TA 100, TA 102, TA 1535, TA 1537, TA 1538). A commercially available duplex system was applied in the experiments emitting an ultrasound beam with a spatial‐peak temporal‐average of 5.2 mW/cm2 and a spatial‐peak temporal‐peak of 117 mW/cm2 at a frequency of 2 MHz. The tester strains were sonicated up to 60 minutes, the bacterial suspension being in direct contact with the transducer surface. The ultrasound‐exposed bacterial suspensions were compared with nonexposed samples. Reference mutagens were used for checking the sensitivity of the system. The results do not indicate any mutagenic effects.