Giemsa banding in the t(13q13q) carrier mother of a translocation trisomy 13 abortus

Summary The abortus of a woman who had had three miscarriages and no normal pregnancies had a 46,XX,D-,t(DqDq)+karyotype. The mother was shown to carry the translocation in balanced state; Giemsa banding demonstrated the abnormal chromosome to be t(13q13q)

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Zusammenfassung Die Abortfrucht einer Frau mit 3 Fehlgeburten und keiner normal ausgetragenen Schwangerschaft hat einen Karyotyp 46,XX,D-,t(DqDq)+.Die Mutter hat die gleiche Translokation im balancierten Zustand. Mit Hilfe der Giemsafärbung erwies sich das abnorme Chromosom als t(13q13q).

     

Quinacrine mustard fluorescence of a second Y chromosome in a Y-autosomal translocation

Summary Screening buccal smears from 97 prisoners by the quinacrine mustard technique revealed one XYY-individual and one Y-autosomal translocation of a second Y chromosome with a 46,XY, D-,t (?15q;Yq)+ karyotype. The translocation chromosome could be identified by its intense fluorescence of the short arm in all 75 metaphases examined.

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Zusammenfassung Untersuchungen von Abstrichen der Mundschleimhaut von 97 Gefängnisinsassen mit der Quinacrine-Mustard-Methode führten zur Aufdeckung eines XYY-Karyotyps und einer Y-autosomalen Translokation eines zweiten Y-Chromosoms mit einem Karyotyp von 46,XY,D-,t(?15q;Yq)+. Das Translokationschromosom konnte durch helle Fluorescenz des kurzen Armes in allen 75 Metaphasen identifiziert werden.

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This work was supported in part by grant number Pa 118/8 from the Deutsche Forschungsgemeinschaft and is part of a thesis by S. F.     

Autoradiographische Identifizierung der an zentrischen Fusionen beteiligten D-Chromosomen bei fünf nichtverwandten Familien: t(14qGq); t(14qGq); t(15qGq); t(13q14q); t(13q15q)

Zusammenfassung Wir berichten über autoradiographische Untersuchungen der D-Chromosomen bei 5 nichtverwandten Familien mit Fusionstranslokationen. Aus der Literatur sind bislang 54 ähnliche Fälle bekannt, die zumeist über klinisch auffällige Individuen entdeckt wurden. Innerhalb dieser Stichprobe ist die Häufigkeit, mit der bestimmte akrozentrische Chromosomen miteinander fusionieren, nicht zufällig. Als mögliche Ursachen werden einerseits die Auswahl der Stichprobe und andererseits einige cytogenetische Mechanismen diskutiert. Erst über auslesefreie cytogenetische Populationsuntersuchungen kann entschieden werden, inwieweit die in der Stichprobe beobachteten Häufigkeiten mit denen in der Durch-schnittsbevölkerung übereinstimmen.

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Autoradiographic identification of D-group chromosomes involved in robertsonian translocation. A study of five unrelated families: t(14qG1); t(14qGq); t(t5qGq); t(13q14q); t(13q15q)

Summary DNA replication studies were carried out on the D-group chromosomes involved in the centric-fusion type chromosomal disorder in members of 5 non-related families. Ascertainement of similiar cases thus far has, almost exclusively, been achieved by investigation of non-balanced carriers. Within a total of 54 patients reported in the literature autoradiography revealed D-acrocentrics to be non-randomly involved. This might be due to ascertainement bias or to endogenous chromosomal mechanisms, as is discussed. It is considered impossible, however, to provide further evidence for the presumed excess of some types of translocation unless selection-free samples have been investigated.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

The densitometric study of G bands on human metaphase chromosomes

Summary The method of densitometric measurement of G bands on human metaphase chromosomes is described, and some factors influencing the densitometric patterns are discussed. The densitometric patterns are reproducible and typical for a given chromosomal pair, although they display some degree of variability. Typical patterns of all human metaphase chromosomes are presented, with the patterns obtained from the measurement of some structurally abnormal chromosomes (t13q14q, t14q21q, Xp-).

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Zusammenfassung Wir beschreiben die Methode der photometrischen Darstellung von G-Banden an menschlichen Chromosomen und diskutieren über einigen Faktoren, die das Resultat beeinflussen. Die photometrischen Kurven sind reproduzierbar und für jedes Chromosomenpaar typisch. Selbstverständlich muß man mit geringen Abstufungen ihrer Variabilität rechnen. Wir zeigen unsere typischen Kurven aller menschlichen Chromosomen, die mit Hilfe der ASG-Technik gefärbt wurden. Gleichzeitig geben wir einige Kurven abnormaler Chromosomen wieder, die auch in unserem Labordargestellt wurden (t(13q14q), t(14q21q), Xp-).

     

New cytogenetic variant of Orbeli's syndrome (46,XY/45,XY,-D/46,XY,Dq+)

Summary A newborn child with multiple congenital abnormalities, including severe hypoplastic thumb and atresia recti, is described. The cytogenetic analysis revealed a mosaicism 46,XY/45,XY,-D/46,XY,Dq+. The combination of mosaic D-monosomy and two cardinal features of 13q-syndrome give the possibility to consider this case as new cytogenetical variant of the Orbeli's syndrome.

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Zusammenfassung Ein Neugeborenes mit multiplen kongenitalen Abnormitäten einschließ-lich erheblicher Hypoplasie der Daumen und Atresia recti wird beschrieben. Die cytogenetische Analyse ergab ein Mosaik 46,XY/45,XY,-D/46,XY,Dq+ Die Kombination von Mosaik D-Monosomie und den zwei Hauptsymptomen des 13q-Syndroms läßt in diesem Falle eine neue cytogenetische Variante des Orbeli-Syndroms vermuten.

     

Identification of two Robertsonian translocations with a Giemsa banding technique

Summary Using a trypsin banding technique a D/D and a G/G translocation were identified as D-13/14 and G-21/22.

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Zusammenfassung Mit Hilfe einer Trypsin-Bandierungstechnik wurde eine D/D-und eine G/G-Translokation als D-13/14 und G-21/22 identifiziert.

     

Short arm deletion of chromosome 14

Summary 3 cases with a Do-chromosome, designated by autoradiography as a No. 14, are presented by the authors. The first case was a mentally retarded boy with minor malformations. Cases 2 and 3 had normal phenotypes and were detected by cytogenetic investigation of family members of a mentally retarded boy with a ring G chromosome. The 14 p-was the only caryotype abnormality in the father (case 2). It was associated with other abnormalities in the daughter (case 3) who had a D/G translocation of the centric fusion type (46, XX, 15-,21-, t(15p21p)+, t(15q21q)+).

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Zusammenfassung 3 Fälle mit einem Dp-Chromosom, das durch Autoradiographie als ein Nr. 14 identifiziert werden konnte, werden dargestellt. In dem ersten Fall bestanden Debilität und unbedeutende morphologische Anomalien. Fall 2 und 3 hatten einen normalen Phänotyp und wurden im Verlaufe von cytogenetischen Untersuchungen von Familienangehörigen eines debilen Jungen mit einem Ring 22 entdeckt. Das 14p-Chromosomwar die einzige Anomalie im Karyoy[ des Vaters (Fall 2). Bei der Tochter (Fall 3) bestand außerdem eine D/G-Translokation (46,XX,15-,21-,t(15p21p)+,t(15q21q)+).

     

Inherited translocations in two families (t(14q+;10q−) and t(13q−;21q+))

Summary Two families with reciprocal translocations (t(14q+;10q–) and t(13q–;21q+)) are described. In both families the proband had multiple congenital anomalies and an unbalanced karyotype, 46,XY,14q+ and 46,XX,21q+ respectively. Routine, autoradiographic and fluorescence techniques were used for analysis of karyotype of probands and their relatives. The probands' phenotypes and the results of their family members' dermatoglyphic analysis are presented in detail.

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Zusammenfassung Zwei Familien mit reziproker Translokation (t(14q+;10q–) und t(13q–;21q+)) werden beschrieben. In beiden Familien weist der Proband multiple angeborene Mißbildungen und einen unbalancierten Karyotyp (46,XY,14q+ bzw. 46,XX,21q+) auf. Für die Analyse aller untersuchten Personen wurden neben der Routine-Methode autoradiographische und Fluorescenz-Methoden verwendet. Die Phänotypen der Probanden sowie die Ergebnisse einer Analyse der Dermatoglyphen bei ihren Familienangehörigen werden genau beschrieben.

     

Chromosomenmosaik 46,XY,D-,t(DqGq)+/92,XYXY,2D-,2t(DqGq)+ bei einem Säugling mit Down-Syndrom

Zusammenfassung Aus kultivierten Lungenfibroblasten eines nach 7 Wochen verstorbenen Säuglings mit den klinischen Zeichen eines Morbus Down konnte ein Chromosomenmosaik diploider und tetraploider Zellen im Verhältnis 2:1 mit zusätzlicher G/D-Translokationstrisomie diagnostiziert werden.Auf Grund morphologischer, cytogenetischer und cytologischer Befunde wird angenommen, daß die tetraploiden Zellen ihren Ursprung vom Ausgangsgewebe, den Explantaten aus der Lunge, genommen haben.

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Chromosome mosaic 46,XY,D-,t(DqGq)+/92,XYXY,2D-,2t(DqGq)+ in fibroblasts of the lung of a baby with Down's syndrome

Summary In a patient with the features common in the Down's syndrome who died after 7 weeks, a chromosome (ploidy) mosaic of diploid and tetraploid cells in a relation of 2:1 and with additional G/D translocation trisomy was present in cultivated fibroblast cells of the lung.From the data of morphological, cytogenetical and cytological investigations it is concluded, that the tetraploid cells originated from the explantates of the lung.

     

Mapping of Aldose Reductase Gene Sequences to Human Chromosomes 1, 3, 7, 9, 11, and 13

Aldose reductase (alditol:NAD(P)+ 1-oxidoreductase; EC 1.1.1.21) (AR) catalyzes the reduction of several aldehydes, including that of glucose, to the corresponding sugar alcohol. Using a complementary DNA clone encoding human AR, we mapped the gene sequences to human chromosomes 1, 3, 7, 9, 11, 13, 14, and 18 by somatic cell hybridization. By in situ hybridization analysis, sequences were localized to human chromosomes 1q32-q42, 3p12, 7q31-q35, 9q22, 11p14-p15, and 13q14-q21. As a putative functional AR gene has been mapped to chromosome 7 and a putative pseudogene to chromosome 3, the sequences on the other seven chromosomes may represent other active genes, non-aldose reductase homologous sequences, or pseudogenes.     

Trisomy 13 with a 13q14q translocation.

A sporadic case of Patau syndrome with 46,XY,14-,t(13q14q)+ karyotype is reported in a 2-month-old child. Dermatoglyphic and cytogenetic findings of the propositus and cytogenetic study of his parents are presented.     

Genetics of Patau's syndrome (an analysis of 59 families)

Different parental translocations were observed in 11 out of 59 families where a child with Patau's syndrome was born. All cases, except for one with t(13; 18) (q14; q23) in the father, revealed the Robertsonian translocations. In most cases there were t(13; 14). The t(13; 15) and t(13; 13) translocations were detected in one mother each. The latter woman bore three babies with Patau's syndrome. One boy in this series had trisomy 13 and sporadic translocation t(2; 22) (q31; q13) simultaneously.     

Unbalanced translocation t(15;22) in "severe" Prader-Willi syndrome

A 13-year-old girl with an unbalanced karyotype 45,XX,-15,der(22)t(15;22)(q13;q13.3) de novo had Prader-Willi syndrome (PWS), (score 13.5), but with features of mental and physical retardation more severe than usually seen in PWS. The clinical diagnosis of PWS was confirmed by methylation analysis that showed absence of the paternal band. With GTG banding, the cytogenetic breakpoint on chromosome 15q13, with 15q14 intact, encompassed the PWS region, while the breakpoint on 22q was terminal. Investigations with FISH utilised ten different probes/combinations, namely SNRPN/PML, TUPLE1/22q13.3, TUPLE/ARSA, GABRB3, three YAC clones and one cosmid for specific regions within chromosome 15q, painting probes for the long arm of chromosomes 15 and 22 and a pantelomere probe. Deletion of SNRPN,TYAC 9 (at 15q11-12), TYAC19 (at 15q13) and GABRB3 (within the PWS locus), was evident on the derivative (22) chromosome, while TYAC10 (at 15q22), cos15-5 (at 15q22) and PML (15q22) were not deleted. On the der(22), 22q13.3 and ARSA were not deleted, but the most distal non specific pantelomeric probe was deleted. Thus, the severe phenotype could be attributable to deletion on chromosome 15q extending beyond q13 to q14, (further than the usual chromosome 15q deletion (q11-13) in PWS), or be related to loss of the very terminal 22q region (from ARSA to the pantelomere) or be due to genetic factors elsewhere in the genome.     

Molecular cytogenetic analysis of follicular lymphoma (FL) provides detailed characterization of chromosomal instability associated with the t(14;18)(q32;q21) positive and negative subsets and histologic progression

We analyzed a cohort of 61 follicular lymphomas (FL) with an abnormal G-banded karyotype by spectral karyotyping (SKY) to better define the chromosome instability associated with the t(14;18)(q32;q21) positive and negative subsets of FL and histologic grade. In more than 70% of the patients, SKY provided additional cytogenetic information and up to 40% of the structural abnormalities were revised. The six most frequent breakpoints in both SKY and G-banding analyses were 14q32, 18q21, 3q27, 1q11-q21, 6q11-q15 and 1p36 (15-77%). SKY detected nine additional sites (1p11-p13, 2p11-p13, 6q21, 8q24, 6q21, 9p13, 10q22-q24, 12q11-q13 and 17q11-q21) at an incidence of >10%. In addition to the known recurring translocations, t(14;18)(q32;q21) [70%], t(3;14)(q27;q32) [10%], t(1;14)(q21;q32) [5%] and t(8;14)(q24;q32) [2%] and their variants, 125 non-IG gene translocations were identified of which four were recurrent within this series. In contrast to G-banding analysis, SKY revealed a greater degree of karyotypic instability in the t(14;18) (q32;q21) negative subset compared to the t(14;18)(q32;q21) positive subset. Translocations of 3q27 and gains of chromosome 1 were significantly more frequent in the former subset. SKY also allowed a better definition of chromosomal imbalances, thus 37% of the deletions detected by G-banding were shown to be unbalanced translocations leading to gain of genetic material. The majority of recurring (>10%) imbalances were detected at a greater (2-3 fold) incidence by SKY and several regions were narrowed down, notably at gain 2p13-p21, 2q11-q21, 2q31-q37, 12q12-q15, 17q21-q25 and 18q21. Chromosomal abnormalities among the different histologic grades were consistent with an evolution from low to high grade disease and breaks at 6q11-q15 and 8q24 and gain of 7/7q and 8/8q associated significantly with histologic progression. This study also indicates that in addition to gains and losses, non-IG gene translocations involving 1p11-p13, 1p36, 1q11-q21, 8q24, 9p13, and 17q11-q21 play an important role in the histologic progression of FL with t(14;18)(q32;q21) and t(3q27).     

Mating between two balanced translocation carriers in two unrelated families

Partial trisomy 9p and a 13/14 translocation occurred in the daughter of a t(5;9)(p15;p12) mother and a t(13;14)(p11;q11) father. Two additional offspring displayed a normal karyotype and a translocation trisomy 13 respectively. Two first cousins, selected for chromosome analysis because of a spontaneous abortion, were found to have an identical translocation t(14;21)(p11;q11). Their second pregnancy was monitored by midtrimester amniocentesis and disclosed a balanced fetus. The different zygotic chromosome constitutions and the counselling problems in the marriages between two balanced translocation carriers are discussed.     

Dicentric and monocentric Robertsonian translocations in man

Summary 5 balanced Robertsonian translocations in man were identified by fluorescence studies. Orcein staining showed two distinct centromeres in 4 of these cases (tdic(13;13), tdic(13;14), tdic(15;21), tdic(21;22)) indicating breaks in the short arms of the involved chromosomes. The dicentric translocation chromosomes were rather stable but monocentrics were noticed in each case. Fluorescence- and measurement studies seemed to indicate that an invisible centromere and part of the short arms were present in these monocentric chromosomes. One case, t(14q21q), was monocentric in all metaphase plates but measurement studies were very suggestive of a visible 21 centromere and incorporation of the invisible 14 centromere (and short arm material) in the long arm of the translocated 14 chromosome, indicating that this translocation originally might have been a real dicentric. Heterochromatin staining was carried out in all cases. The tdic(15;21) showed 6 heterochromatin blocks; 2 of these blocks were probably satellites from chromosome No. 21, visible too in fluorescence. The 4 other translocations showed 4 separated blocks. No differences were observed between monocentrics and dicentrics supporting the theory of a preserved, but invisible centromere in monocentrics.

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Zusammenfassung 5 balancierte humane Translokationen vom Robertson-Typ wurden durch Fluorescenzuntersuchungen identifiziert. Die Orceinfärbung zeigte in 4 dieser Fälle 2 distinkte Zentromere (tdic(13;13), tdic(13;14), tdic(15;21), tdic(21;22)). Dieser Fund ließ es als wahrscheinlich erscheinen, daß der Bruch am kurzen Arm der involvierten Chromosomen stattgefunden hatte. Die dizentrischen Translokationschromosomen waren verhältnismäßig stabil. Es wurden doch monozentrische Chromosomen in allen Fällen beobachtet. Eine Kombination von Fluorescenzuntersuchung und Messung der Chromosomen machte es wahrscheinlich, daß auch in diesen monozentrischen Chromosomen ein unsichtbares Zentromer und Teile der kurzen Arme vorhanden sind. Eine (14q21q)-Translokation hatte in allen Metaphasen nur ein Zentromer. Messungen jedoch deuteten an, daß das 21-Zentromer sichtbar war, daß aber das 14-Zentromer und Material der kurzen Arme am langen Arm des translozierten 14-Chromosoms inkorporiert waren. Das Translokationschromosom ist möglicherweise ursprünglich ein dizentrisches Chromosom gewesen. In allen Fällen wurde eine Heterochromatinfärbung ausgeführt. Die tdic(15;21) hatte 6 Heterochromatinblöcke. 2 davon waren wahrscheinlich die Satelliten des Chromosoms Nr. 21, die auch bei der Fluorescenzmikroskopie sichtbar waren. Die 4 anderen Translokationen hatten 4 separate Blöcke. Monozentrische und dizentrische Chromosomen zeigten hier keinen Unterschied, was die Theorie unterstützt, daß die Zentromere im monozentrischen Chromosomen erhalten, aber unsichtbar sind.

     

Un cas de rétinoblastome bilatéral avec monosomie 13 partielle (q12→q14)

Résumé Une fillette légèrement arriérée mentale, et pratiquement non malformée, est atteinte d'un rétinoblastome bilatéral. Son caryotype leucocytaire montre une monosomie 13 partielle par délétion (q12q14). La synthèse de toutes les observations de rétinoblastome avec délétion du chromosome 13, examinées en techniques de bandes, paraît montrer que le point commun en est la délétion de la bande q14. L'hypothèse pathogénique la plus probable fait appel au phénomène de l' «haplo-insuffisance».

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Summary A partial monosomy 13 by interstitial deletion was found in the complement of a girl with mild mental retardation and bilateral retinoblastoma. Break points were at 13q12 and 13q14. After comparison with other known observations of retinoblastoma with deletion of chromosome 13, it is suggested that the deletion common to these patients may be band 13q14. The most likely pathogenic hypothesis seems to be the haplo-insufficiency.

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Avec la collaboration technique de     

A Somatic Origin of Homologous Robertsonian Translocations and Isochromosomes

One t(14q14q), three t(15q15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly the result of a mitotic exchange.     

Localization of the LDHA gene to 11p14→11p15 by in situ hybridization of an LDHA cDNA probe to two translocations with breakpoints in 11p13

Summary Lymphoblastoid cell lines established from two individuals with apparently balanced translocations involving 11p13 were used for LDHA regional localization. The karyotypes were 46,XY,t(4;11)(q21;p13) and 46,XY,t(1;11) (p22;p13). In situ hybridization of a human LDHA cDNA probe to chromosome preparations from these cell lines resulted in specific labeling over bands p14p15 of the normal chromosomes 11 and over bands 11p1411p15 of the derivative chromosomes 4 and 1. These results exclude LDHA from any region proximal to 11p13 and localize the gene to 11p1411p15.     

Micro RNA, C/D RNA and parental genoming imprinting.

Experimental and computer-assisted approaches have led us to identify hundreds of small non-coding RNA (ncRNAs) whose genes - clustered at two chromosomal domains (the DLK1-GTl2 region/human 15q11q13 and the SNURF-SNRPN/human 14q32 loc) - are subjected to genomic imprinting. Here, we discuss their genomic organization, their expression pattern and their potential functions. A travers des approches in silico et expérimentales, nous avons récemment identifié des centaines de petits ARN non-codants, ARNnc - ARN C/D et microARN - dont les gènes sont soumis à l'empreinte génomique parentale (EGP). Ils sont regroupés au sein de deux loci chromosomiques conservés: le domaine DLK1-GTL2 (locus Callypige, position chromosomique humaine 14q32) et le domaine SNURF-SNRPN (locus Prader-Willi, position chromosomique humaine 15q11q13). Dans cet article, l'organisation génique, le mode d'expression et les fonctions de ces petits ARN sont présentés.