Search

Editor—Hypomelanosis of Ito (HI) (MIM 146150) is an aetiologically heterogeneous physical finding characterised by a swirling pattern of hypopigmentation of the skin, typically distributed along the lines of Blaschko, reflecting pigmentary mosaicism. Chromosomal abnormalities are common and very heterogeneous. They include X;autosomal translocations and mosaicism of aneuploidy, segmental trisomies, or monosomies.1-5 As HI is not a specific disorder, it has also been referred to as pigmentary mosaicism.6 This report adds a further chromosomal anomaly which has not been described in pigmentary mosaicism previously. The proband was the first son born to a 29 year old mother and a 30 year old father. There was no family history of recurrent abortions, consanguinity, or mental retardation. He was born by caesarian section at term after an uncomplicated pregnancy with a weight of 3560 g (50th centile), a length of 50 cm (50th centile), and an occipitofrontal circumference (OFC) of 32 cm (

DiGeorge syndrome (DGS) is a developmental field defect, characterised by absent/hypoplastic thymus and parathyroid, and conotruncal heart defects, with haploinsufficiency loci at 22q (DGS1) and 10p (DGS2). We performed fluorescence in situ hybridisations (FISH) and polymerase chain reaction (PCR) analyses in 12 patients with 10p deletions, nine of them with features of DGS, and in a familial translocation 10p;14q associated with midline defects. The critical DGS2 region is defined by two DGS patients, and maps within a 1 cM interval including D10S547 and D10S585. The other seven DGS patients are hemizygous for both loci. The breakpoint of the reciprocal translocation 10p;14q maps at a distance of at least 12 cM distal to the critical DGS2 region. Interstitial and terminal deletions described are in the range of 10-50 cM and enable the tentative mapping of loci for ptosis and hearing loss, features which are not part of the DGS clinical spectrum.

Mouse synaptonemal complexes (SCs) were hybridized with a telomeric DNA probe. The biotinylated probe was detected with antibodies conjugated to 5-nm colloidal gold and observed in the transmission electron microscope. The distribution of the probe was clearly marked by clusters of the gold particles and the ultrastructure of the SC was not adversely affected by the procedure.

In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.

Summary For >3 decades, Giemsa banding of metaphase chromosomes has been the standard karyotypic analysis for pre- and postnatal diagnostic applications. However, marker chromosomes or structural abnormalities are often encountered that cannot be deciphered by G-banding alone. Here we describe the use of multiplex-FISH (M-FISH), which allows the visualization of the 22 human autosomes and the 2 sex chromosomes, in 24 different colors. By M-FISH, the euchromatin in marker chromosomes could be readily identified. In cases of structural abnormalities, M-FISH identified translocations and insertions or demonstrated that the rearranged chromosome did not contain DNA material from another chromosome. In these cases, deleted or duplicated regions were discerned either by chromosome-specific multicolor bar codes or by comparative genomic hybridization. In addition, M-FISH was able to identify cryptic abnormalities in patients with a normal G-karyotype. In summary, M-FISH is a reliable tool for diagnostic applications, and results can be obtained in ≤24 h. When M-FISH is combined with G-banding analysis, maximum cytogenetic information is provided.

The gene for ubiquitin hydrolase on the X chromosome (UHX1), cloned and mapped to Xp21.2-p11.2, is a candidate gene for retinal diseases. We used fine mapping techniques to localise UHX1 between markers DXS1266 and DXS337, where congenital stationary night blindness (XICSNB) and retinitis pigmentosa type 2 (RP2) are also located. Reevaluation of the UHX1 gene structure demonstrated five new exons, for a total of 21 exons and a predicted protein product of 963 amino acids. Evaluation of patients revealed no UHX1 mutations using SSCP (10 CSNB1 and 20 XLRP) or deletion screening with cDNA hybridisation (13 CSNB1 and 43 XLRP). Likewise, no aberrations were found in the nearby PCTAIRE1 (PCTK1) gene in 13 CSNB1 and 43 XLRP patients by deletion screening. Thus mutations of UHX1, and probably PCTK1, do not appear to cause common X-linked eye diseases. UHX1's role in patients with mental retardation may be appropriate for further investigations into UHX1 function.

A 10-year-old boy with a de novo del(16)(q12.1q13) and many features of the deletion 16q phenotype is described. The deletion occurred in a paternal chromosome as demonstrated by DNA studies with polymorphic (AC)n microsatellite repeat markers. Comparison with published cases suggests that deletion of either of two regions (q13 and q22.1) on the long arm of chromosome 16 is associated with an apparently identical phenotype. No parental imprinting of this region was demonstrated.

DNA libraries from sorted human gonosomes were used selectively to stain the X and Y chromosomes in normal and aberrant cultured human cells by chromosomal in situ suppression (CISS-) hybridization. The entire X chromosome was stained in metaphase spreads. Interphase chromosome domains of both the active and inactive X were clearly delineated. CISS-hybridization of the Y chromosome resulted in the specific decoration of the euchromatic part (Ypter-q11), whereas the heterochromatic part (Yq12) remained unlabeled. The stained part of the Y chromosome formed a compact domain in interphase nuclei. This approach was applied to amniotic fluid cells containing a ring chromosome of unknown origin (47,XY: +r). The ring chromosome was not stained by library probes from the gonosomes, thereby suggesting its autosomal origin. The sensitivity of CISS-hybridization was demonstrated by the detection of small translocations and fragments in human lymphocyte metaphase spreads after irradiation with 60Co-gamma-rays. Lymphocyte cultures from two XX-males were investigated by CISS-hybridization with Y-library probes. In both cases, metaphase spreads demonstrated a translocation of Yp-material to the short arm of an X chromosome. The translocated Y-material could also be demonstrated directly in interphase nuclei. CISS-hybridization of autosomes 7 and 13 was used for prenatal diagnosis in a case with a known balanced translocation t(7:13) in the father. The same translocation was observed in amniotic fluid cells from the fetus. Specific staining of the chromosomes involved in such translocations will be particularly important, in the future, in cases that cannot be solved reliably by conventional chromosome banding alone.

The craniosynostosis syndromes are a heterogeneous group of sporadic, autosomal dominant disorders with significant clinical overlap. Recently, we described a large family with autosomal dominant craniosynostosis suggestive of Saethre-Chotzen syndrome, in which linkage to the Saethre-Chotzen syndrome loci on 7p had been excluded. We now report the presence of a mutation in the fibroblast growth factor receptor 3 (FGFR3) in this family. The mutation, P250R, had been previously reported in 10 patients with non-syndromic craniosynostosis. Variable expression of this mutation is evident especially in two additional members of this family, one of whom is severely affected with pancraniosynostosis. The family provides a further example of genetic heterogeneity and variable expression of the craniosynostosis syndromes and broadens the phenotypic spectrum associated with the FGFR3 mutation P250R. In addition, we found a polymorphism (F384L) in the transmembrane domain of FGFR3 which occurs with a frequency of 3% in the Turkish population but is uncommon among Germans.

From prenatal diagnosis data obtained on mothers aged 35 years and above in the Federal Republic of Germany (DFG data), older fathers are demonstrated to have an increased risk of having trisomy 21 offspring. For paternal ages of 41 years upward, the age effect is quite strong. The risk for a fetus to have any de novo chromosomal aberration increases more with advancing paternal age for older mothers than for younger ones. Thus the ages of both parents have to be taken into account as an indication for prenatal diagnosis. Risk figures for trisomy 21 and for any de novo chromosomal aberration are given, together with preliminary recommendations for prenatal diagnosis for different combinations of parental ages.

Es wird eine Ubersicht uber die verschiedenen Methoden zur DNS-Messung an Chromosomen gegeben. Die Methoden werden kurz beschrieben und die wichtigsten Ergebnisse der verschiedenen Autoren diskutiert.

A hypervariable DNA marker is closely linked to one of the most severe forms of night blindness, X-linked retinitis pigmentosa (RP). Affected individuals with X-linked RP, obligate carriers, and ophthalmologically identifiable carriers of the disease were included in a linkage study. The diagnosis was established in five sibships by funduscopic and electrophysiological investigations. When the X-linked probe M27 beta was used, 2 recombinants out of 29 informative meioses were detected (theta = 0.07 at a maximum lod of 4.75). The hypervariable probe detected two different alleles in 38 of 39 females tested. M27 beta is therefore a potentially very useful probe for carrier detection and prenatal diagnosis, as well as for addressing the question of heterogeneity of X-linked RP.

The observation of a double kidney pelvis with duplication of the ureter, which was found discordant in identical twins is demonstrated.