The tricho-rhino-phalangeal syndrome(s): chromosome 8 long arm deletion: is there a shortest region of overlap between reported cases? TRP I and TRP II syndromes: are they separate entities?

Critical cytogenetic (re)evaluation of 2 of our own cases of tricho-rhino-phalangeal syndrome II (TRP II), or Langer-Giedion syndrome (LGS), and 10 cases from the literature, suggests that the shortest region of overlap of the 8q deletion is a part of band q24.1. This region is assumed to be causally related to this syndrome, and possibly also to TRP I syndrome which, therefore, may not be a causally separate entity.

Premature centromere division: a possible manifestation of chromosome instability.

Retrospective analysis of "routine" chromosome preparations from 2 patients with Fanconi anemia and 2 others with ataxia-teleangiectasia showed increased chromosome breakage and a tendency to premature centromere division (PCD) with special reference to early separation of the large acrocentric (13-15) chromosomes. The findings suggest that PCD may be a manifestation of chromosome instability related to potential malignancy.

Another model for the inheritance of Rett syndrome.

The fact that probably less than 1% of Rett syndrome cases are familial speaks in favor of a spontaneous mutation as the most common cause of Rett syndrome. However, the few familial cases (about 10) described in the literature, the elevated consanguinity rate in parents of Rett patients (2.4% vs. 0.5%), and the existence of "formes frustes" in relatives of Rett girls, suggest that inheritance must exist. A model based on a hypothetical form of inheritance, namely allelic and non-allelic metabolic interference, fits almost all available data, as well as the exclusive occurrence in females without increased abortion rate.

Delineation of a clinical syndrome caused by mosaic trisomy 15.

We report on a boy with mosaic trisomy 15. The clinical manifestations are compared with those of the few cases reported up to now. A clinical syndrome is delineated consisting of a characteristic shape of the nose and other minor craniofacial anomalies, as well as typical deformities of the hands and feet. Different degrees of mosaicism may explain the more or less severe manifestations in individual patients.

Rett syndrome and genetic drift.

An X chromosome gene is assumed to be responsible for the cause of Rett syndrome (RS). However, new genealogical observations suggest involvement of autosomal recessive gene(s) as well, at least in familial cases. To account for these and other recent observations, the theoretical model presented in 1990 by the authors of this paper is applied to the calculation of gene frequencies. Observed frequencies of sporadic and familial cases of RS are used, taking into account genetic drift in inbreeded areas. Moreover, an attempt is made to use the proportion of RS variants in familial and sporadic cases for the explanation of so called 'formes frustes', and as evidence for the existence of female as well as male carriers. The estimated frequency of the recessive autosome mutation, or possibly a frequent polymorphism, is 22.5%.

Presumptive monosomy 21 with neuronal migration disorder re-diagnosed as de novo unbalanced translocation t(18p;21q) by fluorescence in situ hybridisation.

We present clinical and cytogenetic data of a one year old boy with partial monosomy for both 21q and 18p, resulting from a de novo unbalanced translocation. The initial diagnosis of a seemingly full monosomy 21 was revised after fluorescence in situ hybridisation (FISH) with whole chromosome painting probes and a locus-specific chromosome 21 probe. The karyotype was reinterpreted as 45,XY,der(18)t(18;21)(p11.2;q22.1),-21. This karyotype, to our knowledge, has not been previously described. The boy presented with a spectrum of clinical features previously described for (partial) monosomy 18p only, for monosomy 21q only, or for both of these aneusomies. The radiological finding of a neuronal migration disorder with localised polymicrogyria (cortical dysplasia) has not been described for either monosomy before.

Sequence of centromere separation in cultured human amniotic cells.

The sequence of centromere division was analysed in 100 selected late metaphase mitoses of cultured human amniotic cells. The pattern obtained was very similar to that of the previously studied lymphocytes; Chromosomes 18, 12, 17, 5 and X proved to be early dividing, and the acrocentrics were the last to separate in both amniotic cells and blood lymphocytes.

[Roberts-SC phocomelia syndrome]. / Roberts-SC-Phokomelie- oder Pseudothalidomid-Syndrom.

The Roberts-SC phocomelia syndrome is a rare autosomal recessive inherited disorder clinically manifested by tetraphocomelia, pre- and postnatal growth retardation, and craniofacial abnormalities (skull, eyes, lip, and palate), accompanied at times by centromer puffing and splitting, renal abnormalities, heart defect, clitoral or penile enlargement, and bilateral corneal opacities. Mental retardation is common in surviving patients.

Unmasking of heterozygosity by inherited balanced translocations. Implications for prenatal diagnosis and gene mapping.

Phenotypic abnormalities in individuals with balanced chromosome rearrangements can be caused by loss of function at the break points and consequent functional homozygosity for recessive genes. This has obvious implications in prenatal diagnosis. Relevant cases are presented and discussed. Mendelian disorders and possibly also disorders which are under polygenic control may be assigned to certain chromosome regions or bands by means of such translocations. Several assignments have been accomplished lately, the approach being much the same as with deletion mapping.

A synopsis of the human Y chromosome.

Phenotypic features and functions known to depend on the presence of the Y chromosome or the H-Y antigen are discussed in relation to structural anomalies of the Y chromosome and other abnormalities of sexual and somatic development. Recent knowledge about molecular organization of constitutive heterochromatin in relation to the human Y is presented. An attempt is made at assigning different functions, genes and DNA sequences to different regions of the Y chromosome.

The effect of SH-SS transition in the structural organization of mitotic chromosomes.

Human lymphoid cell cultures were treated with 2,2'-dithiodipyridine, a thiol reacting agent which produces SS bridges inside the living cells. After 1 to 4 h treatment chromosome preparations were made. The chromosomes acquired a peculiar segmentation along the chromatids. The results suggest that the alteration might arise from a direct reaction of the agent with special chromosomal proteins. The resistance of treated chromosomes to alkali-heat treatment used in C-banding technique was different from that of untreated chromosomes. This prefixational procedure seems to be advantageous in analysing both the chromosome organization and the banding mechanism.

Incidental finding of double minutes (DM), single minutes (SM), homogenously staining regions (HSR), premature chromosome condensation (PCC), and premature centromere division (PCD)?

The incidental finding of DM's, minutes, HSR's, PCC, and PCD in two completely unrelated cases--one is a prenatal diagnosis in a twin pregnancy complicated by hydramnios and feto-fetal exsanguination, the other is an adult Klinefelter patient--raises the question whether such findings are coincidental or whether there is a common denominator in such cases. Possible relationships between these phenomena and the observed cases are discussed.

A variant of the fra(X) syndrome.

A decondensed site at band q26 of the X chromosome was found in a male baby with growth and developmental retardation and a dysmorphic syndrome, as well as in his pheno-typically normal mother, without using any special culture conditions.

[Translocation trisomy 4q in 2 siblings as a sequela of paternal balanced reciprocal translocation: t(1;4)(q44;q31)]. / Translokationstrisomie 4q bei zwei Geschwistern als Folge einer väterlichen balancierten reziproken Translokation: t(1;4)(q44;q31).

In a sister and a brother with striking similarity of facial dysplasias, severe disturbance of expressive speech, and mild mental retardation a partial trisomy of the long arm of chromosome 4 was identified as cause of these anomalies. The partial trisomy 4q was due to a balanced translocation between the chromosomes 1 and 4 in the father of both children.

Late separating D/D fusions in subjects with "balanced" translocation.

The centromere separation sequence was determined in the mitoses of 5 subjects with "balanced" D/D translocations. Similarly to the acrocentrics, also the D/D fusions belonged to the chromosomes the sister chromatids of which separated last in the late metaphase stage.

Terminal or interstitial deletion in chromosome 8 long arm in Langer-Giedion syndrome (TRP II syndrome)?

Reexamination with high resolution banding of the first ever published case of Langer-Giedion syndrome with 8q deletion as well as chromosome examination of a second case of this syndrome with different high resolution methods, confirmed our previous assumption of a terminal 8q involvement in the causation of TRP II syndrome.

A final word on the tricho-rhino-phalangeal syndromes.

Chromosomal findings in the majority of cases of TRP II (or Langer-Giedion) syndrome and in some cases of TRP I syndrome lead to the conclusion that the former is due to a deletion extending from 8q24.11 to 8q24.13 whereas the latter is caused by an even smaller deleted segment, namely 8q24.12. A case of tricho-rhino-phalangeal syndrome type I with a mosaic deletion of band 8q24.12 is described.

[DNA diagnostics in hemophilia A and B]. / DNA-Diagnostik bei Hämophilie A und B.

Carrier detection and prenatal diagnosis of hemophilia A and B are possible with cloned factor-VIII:C- and factor-IX-gene-specific or linked probes which detect restriction fragment length polymorphisms (RFLPs). In this study, 12 hemophilia-A- and 5 hemophilia-B-families were studied to identify carriers and provide adequate genetic counselling to women who were heterozygous for one or more of the intragenic or linked DNA probes with respect to future pregnancies.