Clinical and molecular analysis of five inv dup(15) patients.

Five patients with inv dup(15) chromosomes were investigated with molecular probes on proximal 15q to determine the parental origin and extent of the duplicated segment. Cytogenetic investigation showed that four patients carried one and a fifth patient had two extra chromosomes derived from number 15 in all cells. In situ hybridization with a chromosome 15 library and a centromere 15 probe confirmed that the entire inv dup chromosomes were derived from chromosome 15. Molecular analysis using probes mapping in the region deleted in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients implied that in at least two patients the extra chromosomes were asymmetric with one copy of the PWS region on the extra marker chromosome but two copies of the region centromeric to the PWS region. Three other cases had an inv dup(15) with two extra copies of the PWS region, but in one of these, heteromorphisms clearly demonstrated that the two centromeres derived from two different chromosomes. The inv dup(15) presumably resulted from an illegitimate recombination event between two different chromosomes 15 in most or all of these cases. All patients showed a maternal origin of the duplicated chromosome. The clinical severity appears to be associated with dosage of the PWS/AS region rather than with differences in the extent of the duplicated segment.

A sporadic form of hereditary neuropathy with liability to pressure palsies: clinical, electrodiagnostic, and molecular genetic findings.

We report a patient who had episodes of recurrent peripheral nerve pressure palsies. Electrodiagnostically, we found a clear decrease of nerve conduction velocity in affected and unaffected nerves. All the patient's relatives showed entirely normal clinical and electrodiagnostic findings. Histopathologically, there were extensive irregularities of the myelin sheaths with numerous tomaculous swellings. DNA analysis revealed a deletion for probes flanking the PMP-22 gene at the maternal chromosome 17 in our patient. His mother showed a normal gene dosage for all markers deleted in our patient, indicating a new mutation.

A new X-linked dysplasia gigantism syndrome: follow up in the first family and report on a second Austrian family.

We report on a new X-linked recessive syndrome in 2 unrelated families, consisting of pre- and postnatal growth excess, typical facial phenotype allowing diagnosis at birth, and usually normal physical and intellectual development. The minor anomalies seen at birth include a "coarse" face with wide nasal bridge, short nose with upturned nasal tip, wide open mouth, thick lips, midline depression of the lower lip, enlarged tongue, highly arched palate, large maxilla and jaw, and a short broad neck. Voice is hoarse and affected individuals have a plump, stocky body with pectus excavatum, thoracic scoliosis, hepatosplenomegaly, umbilical and/or inguinal hernias, broad short hands and feet, and in some cases preauricular dimples, abnormal ears, postaxial hexadactyly, hypoplastic index finger nails, and abnormal dermatoglyphics. Early postnatal death is frequent and pathogenetically unexplained. During infancy and childhood the leading manifestations are the overgrowth (greater than 97th centile), striking facial appearance, hypodontia and/or malposition of teeth, genua valga, hypoplastic calf muscles, and clumsiness. Adolescent and adult patients have well proportioned "gigantism" of athletic build (192-210 cm), large "coarse" face, and a deep voice. General intellectual and motor development are either normal or mildly delayed. Results of routine laboratory tests are normal, as are growth hormone and IGF I levels and chromosomes. Pathogenesis remains unknown. Heterozygotes may show some of the characteristic facial changes.

Ankylosing spondylitis: cauda equina syndrome with multiple spinal arachnoid cysts. Case report.

A case of ankylosing spondylitis in a patient with a cauda equina syndrome is reported. A lumbar myelogram revealed erosions of the bones of the neural canal with enclosed multiple intraspinal cysts.

[Prenatal diagnosis: results and observations (author's transl)]. / Ergebnisse und Erfahrungen bei der pränatalen Diagnose.

In a period of over 7 years, 57 pathological results were obtained on analysis of 1470 amniotic fluid samples. The findings are tabulated in this paper and attention is drawn to the importance of the demonstration of rapidly adherent neural cells and specific neurogenic acetyl cholinesterase in the amniotic fluid in the diagnosis of open neural defects. Experience gained in this field is the basis for suggested guide lines applicable to prenatal diagnostic centres.

[Clinical importance of chromosomal translocations (author's transl)]. / Klinische Bedeutung chromosomaler Translokationen.

5835 chromosomal analyses were performed between May 1, 1962 and December 31, 1978. We found 68 translocations (1.1%). 36 translocation carriers were identified as being chromosomally balanced, of whom 24 were healthy and 12 clinically abnormal (5 showed centric fusions - 3 x D/D, 2 x D/G - and 7 other chromosomal rearrangements). 32 translocation carriers were chromosomally non-balanced, among them 28 patients with centric fusions (12 x G/G, 2 x D/D, 14 x D/G) and 4 with other rearrangements combined with characteristic clinical features. A review of the chromosomal translocations found in our laboratory is presented. The relation between clinical appearance and chromosomal rearrangement is discussed.

[A 5-year review of prenatal diagnosis in Graz (author's transl)]. / 5 Jahre pränatale Diagnose in Graz.

Between 1/7/1974 and 30/6/1979 we analysed 532 amniotic fluid cell cultures. In 402 cases a genetic indication for amniocentesis was given; 57 prenatal diagnoses were carried out for gynaecological and other medical indications. We also analysed 73 amniotic fluid test samples. Altogether 19 pathological results (3.6%) were found. We observed 16 abnormal findings in 459 diagnostic amniocenteses and 3 pathological results in the test cultures. The transmission of parental chromosomal polymorphisms to the fetus is discussed here. The importance of prenatal diagnosis in genetic counselling, along with cost-benefit reflections, are stressed in this paper.

Molecular and clinical findings in Austrian cystic fibrosis patients with mutations in exon 11 of the CFTR gene.

In order to determine the heterogeneity of mutations in exon 11 of the cystic fibrosis transmembrane conductance regular (CFTR) gene in Austrian cystic fibrosis (CF) patients, we analysed 207 non-delta F508 chromosomes by direct sequencing of PCR-amplified genomic DNA. A total of four previously described point mutations present on 14/207 (6.8%) non-delta F508 chromosomes were detected: G542X, G551D, R553X, and R553Q. The second CF mutation was delta F508 in most patients, W1282X (a nonsense mutation in exon 20) in one and a currently unknown non-delta F508 mutation in another case. One patient was documented to be homozygous for G542X. The proportion of non-delta F508 chromosomes among total CF chromosomes is 45% in Austria and 32% in the world population. In our population the mutations G542X, G551D, and R553X were found on 3.9% (1.7%), 1.9% (0.9%) and 0.5% (0.2%) of non-delta F508 chromosomes (of total CF chromosomes), respectively. The average worldwide frequencies of these mutations are higher: 7.1% (2.4%), 4.8% (1.6%), 2.1% (0.7%) of non-delta F508 chromosomes (of total CF chromosomes screened), respectively. A comparison of the allele frequencies in Austria with those detected in neighbouring countries reveals some notable differences. In a subsequent retrospective analysis we found that all nucleotide changes, identified by direct sequencing, can be detected by denaturing gradient gel electrophoresis (DGGE). The lack of any false positive or false negative result suggests that DGGE is a convenient and reliable screening method for point mutations.

[Chromosome analysis in abortion]. / Chromosomenanalysen bei Abortus.

Many spontaneous abortions are caused by chromosome abnormalities of zygotes or embryos. We found chromosome aberrations in 15 of 59 successful cultivated tissues of miscarriages. The detecting of one trisomy 2 in these investigations is remarkable. At the same time we examined the chromosomes of couples suffering from repeated abortions. 21 of 512 tested females and 12 of 474 tested males showed abnormal chromosome sets. The results and their consequences are discussed.

[Immunomodulator action of living, nonpathogenic Enterococcus faecalis bacteria from humans]. / Immunmodulatorische Wirkung lebender nicht-pathogener Enterococcus faecalis-Bakterien des Menschen.

Immunomodulating Effect of Living Nonpathogenic Enterococcus faecalis Originated from Humans Symbioflor 1 is a pharmaceutical preparation, consisting of a suspension of living nonpathogenic Enterococcus faecalis (E. faecalis). The effect on the liberation of cytokines of E. faecalis was investigated in in-vitro experiments with human peripheral mononuclear blood cells revealing the following results: 1. E. faecalis stimulates the liberation of interleukin 1 (IL-1 beta) and interleukin-6 (IL-6) in a dose-dependent manner; the E. faecalis induced liberation of IL-1 beta and IL-6 is inhibited by dexamethasone (Dm) but not by cyclosporin A (CsA). 2. E. faecalis stimulates the liberation of gamma-interferon (IFN-gamma) in a dose-dependent manner, which is inhibited by both Dm and CsA. 3. Phytohemagglutinin (PHA)-induced liberation of gamma-IFN and interleukin-2 (IL-2) is inhibited by E. faecalis in a dose-dependent manner. The relevancy to clinical trials of the in vitro results is discussed.

Frequency of delta F508 and haplotype association in Austrian cystic fibrosis families.

The frequency of the major mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene was analyzed for 113 Austrian cystic fibrosis (CF) patients. An overall frequency of 55% for delta F508 was found with values of 72% and 13% for patients with pancreatic insufficiency (CF-PI) and those with pancreatic sufficiency (CF-PS), respectively. Furthermore, the distribution of the alleles of the closely linked DNA markers XV2c/KM19/MP6d-9 in our families is described.

High resolution banding of an unusual reciprocal translocation in recurrent abortions.

Reciprocal translocations involving two chromosomes frequently cause abortion of unbalanced offspring. In many cases, however, meiosis leads to a cytogenetically normal or balanced gamete with normal embryonal development. In a couple investigated because of recurrent reproductive loss, the husband had a reciprocal exchange of parts of the long arms of chromosomes 9 and 10 in the form of inverted insertions. Due to difficulties in obtaining regular homologous pairing during zygotene, this anomaly might not be compatible with cytogenetically normal or balanced offspring. The diagnosis of this translocation was possible using a previously published alkaline Giemsa G-banding technique.

A new X-linked dysplasia gigantism syndrome: identical with the Simpson dysplasia syndrome?

Thirteen male newborns of a family spanning five generations revealed a syndrome consisting in elevated birth weight and length, a disproportionately large head with coarse, distinctive facies, short neck, slight obesity, and broad, short hands and feet. The affected who reached adulthood attained heights of about 2 m; their unusual facial and general appearance and the clumsiness of all their motions, remarkable during infancy and childhood, had become somewhat less conspicuous. In all but one affected individual, intellectual development was normal. In two index cases neither clinical nor laboratory evaluations revealed a basic defect. X-linked recessive inheritance is most probable.

A comparative analysis of the karyotypes of Cricetus cricetus and Cricetulus griseus.

This study presents a comparison of the mitotic chromosomes of the two species of hamsters Cricetus cricetus (European hamster) and Cricetulus griseus (Chinese hamster), which have the same chromosome number of 2n=22.--G-banding procedure reveals striking similarities in both karyotypes and gives the possibility to analyse structural changes so that two examples for Robertsonian rearrangement can be observed.--A remarkable kind of difference between the two karyotypes becomes obvious after C-banding procedure. While Cricetus cricetus shows a large amount of predominantly centromeric heterochromatin, in Cricetulus griseus C-bands are less conspicuous, and a few chromosomes do not exhibit any centromeric heterochromatin at all.

Studies on sex chromosomes of four hamster species: Cricetus cricetus, Cricetulus griseus, Mesocricetus auratus, and Phodopus sungorus.

In this paper, we present an analysis of the sex chromosomes of four hamster species after application of different staining techniques. The mitotic X chromosomes show a striking similarity in G-banding pattern but rather great differences in their C-banding patterns. A presumably homologous euchromatic segment that exhibits two distinct G-bands appears in the X chromosome of each species. The Y chromosome of Cricetus cricetus is in contrast to those of the other species, because it reveals a relatively well-differentiated G- and C-banding pattern. In meiotic metaphase I, interstitial chiasmata can be found in the sex bivalents of Cricetus cricetus and Cricetulus griseus, whereas the gonosomes of Mesocricetus auratus and Phodopus sungorus sungorus are terminally associated. The regions that are involved in pairing or association are always heterochromatic.