Walter Rosenkranz

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

SummaryThirteen 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.

Die bedeutung der Assoziation satellitentragender Chromosomen

SummaryIt has been postulated that the association of satellited chromosomes is of aetiological interest with respect to chromosomal aberrations. For this reason an investigation was carried out to determine its frequency in blood cultures of healthy adult persons, in nonmongoloid children and in mongoloid children with trisomy 21. The mean of 45 cultures of 15 healthy male probands was 32,6±14,7 associations per 100 mitoses; that of 15 healthy female probands 39,2±12. Variance analysis proved the considerable standard deviation to be mostly due to individual than to differences between parallel cultures of a given proband. In several instances the determinations were repeated which showed that the frequency of associations of satellited chromosomes appears to be individually specific and relatively stable. The frequency is being influenced by the methods of culturing. The mean out of 10 male mongoloid children was found to be 49,5±18,6 associations per 100 mitoses; 10 female mongoloid children showed a frequency of 58,9±16,9. In 15 non-mongoloid children with an age distribution similar to that of the mongoloid cases the mean out of 30 cultures was 27,2±15,3 associations per 100 mitoses. The difference between the means of mongoloid and non-mongoloid children appears to be significant (P<0,001); the augmented number of chromosomes in trisomy 21 (plus one) has been properly considered. Besides this, the variability of the different patterns of associations have been calculated. In all groups the obtained values of distribution deviated significantly from the ones to be expected: there was a constant decrease in D-D and an increase in G-G association patterns. The G-chromosome seemed to have greater tendency toward association than the chromosomes of group D. The findings, their possible aetiology and their implications are being discussed.ZusammenfassungDer Assoziation satellitentragender Chromosomen soll eine ätiologische Bedeutung bei der Entstehung von Chromosomenaberrationen zukommen. Es wurde daher ihre Häufigkeit in Blutkulturen von gesunden erwachsenen Personen, von nichtmongoloiden Kindern und von mongoloiden Kindern mit Trisomie 21 bestimmt und die Häufigkeitswerte der Versuchsgruppen miteinander verglichen. Der Mittelwert aus 45 Kulturen von 15 gesunden Männern betrug 32,6±14,7 Assoziationen/100 Mitosen, der von 15 gesunden Frauen 39,2±12,0. Durch Varianzanalyse wurde nachgewiesen, daß die große Streuung vor allem durch individuelle Schwankungen und weniger durch Unterschiede zwischen parallellaufenden Kulturen einer Versuchsperson bedingt ist. Bei einigen Personen wurden die Untersuchungen mehrfach wiederholt und dadurch wahrscheinlich gemacht, daß die Satellitenassoziations-häufigkeit individualspezifisch und relativ stabil ist. Sie wird durch die Kulturart beeinflußt. Der Mittelwert aus 20 Kulturen von 10 mongoloiden Knaben war 49,5±18,6 Assoziationen pro 100 Mitosen und der von 10 mongoloiden Mädchen 58,9±16,9. Von 15 nichtmongoloiden Kindern mit ähnlicher Altersverteilung wie bei den mongoloiden war der Mittelwert aus 30 Kulturen 27,2±15,3 Assoziationen/100 Mitosen. Die Differenz zwischen dem Mittelwert der mongoloiden und dem der nichtmongoloiden Kinder ist mit P<0,001 signifikant, dabei wurde die um 1 vermehrte Zahl der satellitentragenden Chromosomen bei der Trisomie 21 berücksichtigt. Neben der Assoziationshäufigkeit wurde auch die Verteilung der Assoziationsmuster (D-D, D-G, G-G) sowie die Beteiligung von D-und G-Chromosomen an Assoziationen ermittelt. Die beobachteten Werte wurden mit den zu erwartenden verglichen. Bei allen Versuchsgruppen wich die beobachtete Verteilung signifikant von der zu erwartenden ab, es waren immer zuwenig D-D- und zuviel G-G-Assoziationsfiguren vorhanden. Die G-Chromosomen scheinen eine höhere Assoziationsneigung zu besitzen als die Chromosomen der Gruppe D. Die dargelegten Befunde, ihre Ursache und Bedeutung werden diskutiert.

Molecular and cytogenetic analysis in two patients with microdeletions of 7p and Greig syndrome: Hemizygosity for PGAM2 and TCRG genes

Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder that has been mapped to 7p13. We have investigated two patients with GCPS and a cytogenetically visible microdeletion of the short arm of chromosome 7 with gene probes that have been assigned close to the proposed Greig locus. Deletion breakpoints were determined from high-resolution G- and R-banded chromosomes. In patient BC with a de novo deletion (7p12.3-7p14.2) we have found a loss of the genomic region containing the T-cell receptor gamma (TCRG) gene cluster, whereas the other patient IR with a deletion (7p11.2-7p13) due to a de novo translocation was apparently normal for this region. Gene dosage analysis revealed a loss of the phosphoglycerate mutase muscular form (PGAM2) gene locus in both patients. Hox 1.4 and interferon-beta 2 (IFNB2) showed a normal gene dosage. Our investigations revealed the following ordering and assignments of the studied genes: PGAM2 and GCPS in 7p12.3-13; TCRG in the distal part of 7p13-7p14.2; Hox 1.4 and IFNB2 distal to 7p14.2. Our results suggest a location of the TCRG gene more proximal than that reported previously. Furthermore, we were able to exclude the Hox 1.4 gene from involvement in the pathogenesis of GCPS.

Distribution of human adult lactase phenotypes in the population of Austria

SummaryA total of 528 unrelated, apparently healthy, adult and adolescent Austrians (270 females, 258 males, mean age 22.1 years) were examined for lactose absorption capacity employing a noninvasive field test based on breath hydrogen (H2) determination. Subjects exhibiting a change of breath hydrogen concentration of less than 15 volumes per million (vpm) after a load of 50 g lactose (n=422) were classified as lactorse absorbers, 106 probands (20.1%) showing increases of breath hydrogen concentration between 16 and 111 vpm were diagnosed as lactose malabsorbers. The distribution of the lactase phenotypes was independent of age and sex. Intolerance symptoms after lactose administration were significantly more frequent in lactose malabsorbers. Grouping of probands according to the birth-places of their grandparents revealed significant differences in the distribution of the lactase phenotypes in East and West Austria (East 25%, West 15% lactose malabsorbers). These differences are discussed in the light of the population history of these regions.

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.

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.

Comparison of Chromosome Banding Patterns in Five Members of Cricetinae with Comments on Possible Relationships

SUMMARYFive species of Cricetinae were investigated with regard to chromosome banding pattern homology. The strikingly coincident G-banding patterns present in Cricetus cricetus and Cricetulus griseus could not be found in the other species. Only Phodopus sungorus shows a still considerable number of homologous segments of chromosomes. The C-banded karyotypes reveal fundamental differences in amount and distribution of heterochromatin. The highest amounts of heterochromatin are found in Cricetus cricetus and Mesocricetus auratus, the lowest amount is shown by Mystromys albicaudatus. The karyotype of Cricetus cricetus is characterized by large blocks of centromeric heterochromatin, that of Mesocricetus auratus by totally heterochromatic short arms of many chromosomes. Cricetulus griseus and Phodopus sungorus possess several pairs of chromosomes without distinct centromeric heterochromatin. Each autosome of Mystromys albicaudatus reveals a small amount of heterochromatin in the centromeric region; two pairs...

Uniparental Origin of Sex Chromosome Polysomies

The parental origin of the additional sex chromosomes in 8 cases with high-order sex chromosome polysomies was determined using DNA polymorphisms. The additional sex chromosomes were paternally derived in 3 48,XXYY cases, and maternal in origin in 1 48,XXXY case and 4 49,XXXXY cases. Thus, all extra chromosomes, within a particular patient, were always derived from only one parent. Their most likely origin was successive nondisjunction at the first and second meiotic division in one germ cell. The mechanism involved remains unclear, but appears to be independent of parental ages.

Homozygous duplication on long arm of chromosome pair no. 1

SummaryIn members of a family it was found, that the long arms from one or both chromosomes A1 are lengthened. The elongation of the chromosomes was caused by duplication of the paracentric region as shown by Giemsa banding pattern.ZusammenfassungBei mehreren Mitgliedern einer Familie wurde eine Verlängerung der langen Arme eines oder beider Chromosomen A1 beobachtet. Dem Giemsa-Bändermuster zufolge dürfte eine Duplikation des zentromerennahen Abschnittes vorliegen.