Showing papers on "Ring chromosome published in 1996"
TL;DR: A translocation, t(17;22)(q22;q13), was identified in two cases of dermatofibrosarcoma protuberans (DP), which casts light on the development and significance in DP of ring chromosomes which consistently harbor sequences derived from chromosomes 17 and 22.
Abstract: A translocation, t(17;22)(q22;q13), was identified in two cases of dermatofibrosarcoma protuberans (DP). They bring to four the number of DP cases characterized by an identical t(17;22)(q22;q13), which can be considered as a new tumor-associated chromosome rearrangement. To date, this translocation has been found only in DP and its juvenile form, giant-cell fibroblastoma. This finding has two major consequences. First, it casts light on the development and significance in DP of ring chromosomes which consistently harbor sequences derived from chromosomes 17 and 22. Second, the identification of this new chromosome marker, and eventually of the underlying molecular rearrangement, should help to classify DP, a soft-tissue tumor of still uncertain cell origin. In addition, it could be used to differentiate DP from truly benign or malignant entities, in order that this tumor of intermediate malignancy could be adequately managed.
187 citations
TL;DR: Findings show that gain of 12q13–15 sequences is a characteristic feature of POS and that these sequences are contained within the ring chromosomes.
Abstract: Seven parosteal osteosarcoma (POS) samples, six of which were cytogenetically characterized, were studied by using comparative genomic hybridization (CGH). All samples showed DNA sequence copy number changes (mean, six aberrations/tumor; range, 1-13); gains were more frequent than losses. Gain of 12q13-15 sequences was found in every tumor and correlated with the presence of ring chromosomes. High-level amplification, which was detected in four tumors, was seen only in chromosome 12, with 12q13-14 as the minimal common region. By using chromosome painting, one of the rings of one case was shown to be composed entirely of chromosome 12 material. Together with previous data, our findings show that gain of 12q13-15 sequences is a characteristic feature of POS and that these sequences are contained within the ring chromosomes.
93 citations
TL;DR: The study suggested a correlation between the percentage of abnormal cells and an abnormal phenotype, and for mosaicism involving a terminal deletion, the possibility of a familial fragile site should be considered.
Abstract: Among 179,663 prenatal diagnosis cases collected from ten institutions and two publications, 555 (0.3 per cent) were diagnosed as having chromosome mosaicism. Of these, 57 (10.3 per cent) were mosaic for an autosomal structural abnormality, 28 (5 per cent) for a sex chromosome structural abnormality, and 85 (15.3 per cent) were mosaic for a marker chromosome. Ninety-five cases of prenatally diagnosed mosaicism with a structural abnormality in an autosome and a normal cell line, and with a known phenotypic outcome, were collected for karyotype-phenotype correlations through our collaboration (40 cases), a prior survey (26 cases), and published reports (29 cases). They included 13 balanced reciprocal translocations, one unbalanced reciprocal translocation, four balanced Robertsonian translocations, four unbalanced Robertsonian translocations, four inversions, 17 deletions, three ring chromosomes, 19 i(20q), seven +i(12p), six other isochromosomes, and 17 partial trisomies resulting from a duplication or other rearrangement. All cases mosaic for a balanced structural rearrangement resulted in a normal phenotype. All cases of 46/46,i(20q) resulted in normal liveborns. Five of seven cases with 46/47,+i(12p) had an abnormal phenotype compatible with Killian-Pallister syndrome. The overall risk for an abnormal outcome for a mosaic case with an unbalanced structural abnormality, excluding 46/46,i(20q) and 46/47,+i(12p), is 40.4 per cent. In the same category, the study also suggested a correlation between the percentage of abnormal cells and an abnormal phenotype. For mosaicism involving a terminal deletion, the possibility of a familial fragile site should be considered.
92 citations
TL;DR: Linkage and segregation analysis in the family suggests that the 12-cM region between D18S51 and D 18S61 located at 18q21.33-q23 may contain a candidate gene for BP illness, and links to chromosome 18 could not be excluded.
73 citations
TL;DR: The parental origin of the ring chromosome in several patients was associated with phenotypes that are also seen in patients with either Prader-Willi or Angelman syndromes, conditions that result from uniparental expression of genes on chromosome 15.
Abstract: Individuals with a ring 15 chromosome [r(15)] and those with Russell-Silver syndrome have short stature, developmental delay, triangular face, and clinodactyly. To assess whether the apparent phenotypic overlap of these conditions reflects a common genetic cause, the extent of deletions in chromosome 15q was determined in 5 patients with r(15), 1 patient with del 15q26.1-qter, and 5 patients with Russell-Silver syndrome. All patients with Russell-Silver syndrome were diploid for genetic markers in distal 15q, indicating that Russell-Silver syndrome in these individuals was unlikely to be related to the expression of single alleles at these or linked genetic loci. At least 3 distinct sites of chromosome breakage close to the telomere were found in the r(15) and del 15q25.1-qter patients, with 1 r(15) patient having both a terminal and an interstitial deletion. Although the patient with del 15q25.1-qter exhibited the largest deletion and the most profound growth retardation, the degree of growth impairment among the r(15) patients was not correlated with the size of the deleted interval. Rather, the parental origin of the ring chromosome in several patients was associated with phenotypes that are also seen in patients with either Prader-Willi (PWS) or Angelman (AS) syndromes, conditions that result from uniparental expression of genes on chromosome 15. In fact, unequal representation of chromosome 15 alleles in 1 patient with r(15) suggests the possibility that a mosaic karyotype composed of the constitutional cell line and cell line(s) possibly deficient in the ring chromosome might be present. The PWS-like or AS-like phenotypes could be explained by postzygotic loss of the ring chromosome, leading to uniparental inheritance of the intact chromosome in some tissues of r(15) patients.
50 citations
TL;DR: The clonal telomeric fusions of 4p with 22q, recurring tas of 11p, and the subsequent loss of the short arm of 11 demonstrated here, suggests that some chromosome regions are subject to nonrandom instability and sometimes loss.
48 citations
TL;DR: It is suggested that the degree to which submicroscopic deletions of chromosome 7 extend beyond the elastin locus may explain some of the phenotypic variability found in Williams-Beuren syndrome.
Abstract: Fluorescence in situ hybridisation (FISH) and conventional chromosome analysis were performed on a series of 52 patients with classical Williams-Beuren syndrome (WBS), suspected WBS, or supravalvular aortic stenosis (SVAS). In the classical WBS group, 22/23 (96%) had a submicroscopic deletion of the elastin locus on chromosome 7, but the remaining patient had a unique interstitial deletion of chromosome 11 (del(11)(q13.5q14.2)). In the suspected WBS group 2/22 (9%) patients had elastin deletions but a third patient had a complex karyotype including a ring chromosome 22 with a deletion of the long arm (r(22)(p11-->q13)). In the SVAS group, 1/7 (14%) had an elastin gene deletion, despite having normal development and minimal signs of WBS. Overall, some patients with submicroscopic elastin deletions have fewer features of Williams-Beuren syndrome than those with other cytogenetic abnormalities. These results, therefore, emphasise the importance of a combined conventional and molecular cytogenetic approach to diagnosis and suggest that the degree to which submicroscopic deletions of chromosome 7 extend beyond the elastin locus may explain some of the phenotypic variability found in Williams-Beuren syndrome.
46 citations
Journal Article•
TL;DR: The results show that cis inactivation does not invariably occur in human females with two X chromosomes, even when the XIC region is present on both of them, and support the hypothesis that the X chromosome counting mechanism involves chromosomal imprinting, occurs prior to the onset of random inactivation, and is required for subsequent inactivation of the chromosome.
Abstract: We have previously reported functional disomy for X-linked genes in females with tiny ring X chromosomes and a phenotype significantly more abnormal than Turner syndrome. In such cases the disomy results from failure of these X chromosomes to inactivate because they lack DNA sequences essential for cis X inactivation. Here we describe a novel molecular mechanism for functional X disomy that is associated with maternal isodisomy. In this case, the severe mental retardation and multiple congenital abnormalities in a female with a mosaic 45,X/ 46,X,del(X)(q21.3-qter)/ 46X,r(X) karyotype are associated with overexpression of the genes within Xpter to Xq21.31 in many of her cells. Her normal X, ring X, and deleted linear X chromosomes originate from the same maternal X chromosome, and all are transcriptionally active. None expresses X inactive specific transcript (XIST), although the locus and region of the putative X inactivation center (XIC) are present on both normal and linear deleted X chromosomes. To our knowledge, this is the first report of a functional maternal X isodisomy, and the largest X chromosome to escape inactivation. In addition, these results (1) show that cis inactivation does not invariably occur in human females with two X chromosomes, even when the XIC region is present on both of them; (2) provide evidence for a critical time prior to the visible onset of X inactivation in the embryo when decisions about X inactivation are made; and (3) support the hypothesis that the X chromosome counting mechanism involves chromosomal imprinting, occurs prior to the onset of random inactivation, and is required for subsequent inactivation of the chromosome.
45 citations
42 citations
TL;DR: Analysis of patients with malignant fibrous histiocytoma revealed that 19p + may be an independent marker of unfavorable outcome in MFH, and there was a trend suggesting fewer relapses after tumors with ring chromosomes.
Abstract: In this study, we examined the relationship of 19p13 aberrations, usually leading to addition of unknown material (19p+), and ring chromosomes to clinical outcome in patients with malignant fibrous histiocytoma (MFH). Analysis of 69 MFHs revealed 19 tumors with 19p+ and 24 tumors with ring chromosomes. After a median follow-up period of 36 months, 24 patients developed metastases, and 27 patients developed local recurrences. Ten patients had both local recurrences and metastases. Local recurrence was more common in association with 19p+ than without. Metastasis was more common with 19p+ tumors in high-risk patients (tumor size > 5 cm and grade III-IV; n = 48) than those without 19p+. There was a trend suggesting fewer relapses after tumors with ring chromosomes. 19p+ may be an independent marker of unfavorable outcome in MFH.
38 citations
TL;DR: Ch Chromosomal organization in interphase nucleus appears to promote the formation of more intra-changes than inter-changes following X-irradiation, most probably due to close proximity of the two arms of a chromosome.
Abstract: Frequencies of intra-chromosomal exchanges (pericentric inversions and centric rings) and inter-chromosomal exchanges (dicentrics and translocations) in X-irradiated (2.5 Gy) human lymphocytes have been estimated. To detect these events we employed FISH (fluorescence in situ hybridization) technique and arm specific painting probes for chromosomes #1 and #3. The ratio between centric rings and pericentric inversions was found to be about 1. For intra-changes to inter-changes, the ratio (F) was between 6 and 9. Based on the total number of colour junctions involving chromosomes #1 and #3 it was found that exchanges between the arms of the same chromosome occur about 8.7 times more than inter-chromosomal exchanges calculated on the basis of the DNA content of the chromosomes and random induction of aberrations in the total genome. Chromosomal organization in interphase nucleus appears to promote the formation of more intra-changes than inter-changes following X-irradiation, most probably due to close proximity of the two arms of a chromosome.
TL;DR: It is concluded that duplication of 12q sequences may be a sufficient level of amplification for development of the microscopic appearance that characterizes ALT.
Abstract: Ordinary lipomas are cytogenetically characterized by a variety of balanced rearrangements involving chromosome segment 12ql3-15, and atypical lipomatous tumors (ALT) by supernumerary ring chromosomes or giant markers known to contain amplified 12q sequences. In a series of 228 cytogenetically analyzed and histopathologically reexamined ordinary lipomas and ALT, 10 tumors showed unbalanced chromosome-12 aberrations. All 4 tumors with loss of segments from 12q were classified as ordinary lipomas, whereas 5 of the 6 tumors showing gain of 12q material were diagnosed as ALT. One or three extra copies of 12q15-q24 were present in all 5 ALT. We conclude that duplication of 12q sequences may be a sufficient level of amplification for development of the microscopic appearance that characterizes ALT.
TL;DR: To the authors' knowledge, this is the first reported patient with an extra ring chromosome derived from chromosome 10p, and it was found in 66% of lymphocytes on routine cytogenetic examination.
Abstract: We present a case with a small extra ring chromosome which was found in 66% of lymphocytes on routine cytogenetic examination. FISH analyses, using centromere specific and single copy probes, showed that the extra ring chromosome was derived from the most proximal part of 10p, close to the centromere. The patient has a unilateral cleft lip and palate, mild dysmorphic features, and mild mental retardation. Only a limited number of extra ring chromosomes have been characterised so far. To our knowledge, this is the first reported patient with an extra ring chromosome derived from chromosome 10p.
TL;DR: In this article, a female baby with multiple congenital anomalies including left upper amelia, congenital short bowel with malrotation and pseudo-obstruction, dextrocardia with situs solitus, patent ductus arteriosus, and a tiny atrophic spleen.
Abstract: We report a female baby with multiple congenital anomalies including left upper amelia, congenital short bowel with malrotation and pseudo-obstruction, dextrocardia with situs solitus, patent ductus arteriosus, and a tiny atrophic spleen. Chromosome study showed de novo 46,XX/46,XX,-4, + r(4)(p16-->q22.3)/47,XX,4, + r(4) (p16-->q22.3), + del(4)(pter-->q22.3:). The clinical findings in the patient were probably caused by the interaction of partial trisomy 4pter-->q22.3 or 4p16-->q22.3 and partial monosomy of 4q22.3-->4qter. This karyotype and phenotype have not previously been reported.
TL;DR: This case and a similar one recently reported demonstrate that acentric fragments can acquire a new centromere and become stable, and that supernumerary marker chromosomes can also originate by the junction of the acentric portions distal to the centric region forming a ring.
Abstract: A ring chromosome 3 and a 47th chromosome formed by the portions of 3p and 3q distal to the r(3) breakpoints were found in a girl with mental retardation and minor facial anomalies. The supernumerary chromosome 3, rea(3), had a primary constriction inside its 3p portion (3p23) and was consistently stable both in lymphocytes and fibroblasts. In situ hybridization with alphoid probes revealed that the r(3) maintained its wild-type centromere, whereas the rea(3) showed no alphoid-related signals. This case and a similar one recently reported demonstrate that acentric fragments can acquire a new centromere and become stable, and that supernumerary marker chromosomes can also originate by the junction of the acentric portions distal to the centric region forming a ring. The possibility of such a chromosome segregating will depend on its ability to (re)activate a new centromere.
TL;DR: This is the first reported occurrence of mood disorder in a person with ring chromosome 22, and case reports describing behavioural problems associated with this chromosome disorder suggest that severe hyperactivity is typical and that affected individuals may have an excited mood state.
Abstract: The case of a 21-year-old man with severe developmental disabilities, ring chromosome 22 and rapid-cycling bipolar illness is presented. This is the first reported occurrence of mood disorder in a person with ring chromosome 22. Previously published case reports describing behavioural problems associated with this chromosome disorder suggest that severe hyperactivity is typical and that affected individuals may have an excited mood state. These symptoms are consistent with atypical bipolar disorder and raise the possibility that ring chromosome 22 increases the risk for atypical bipolar disorder.
TL;DR: A newborn infant, who presented with macrocephaly, asymmetric square skull, minor facial anomalies, omphalocele, inguinal hernias, hypospadias, and club feet, is identified with a karyotype with an interstitial deletion and a marker chromosome formed from the deleted segment.
Abstract: Karyotypes with an interstitial deletion and a marker chromosome formed from the deleted segment are rare. We identified such a rearrangement in a newborn infant, who presented with macrocephaly, asymmetric square skull, minor facial anomalies, omphalocele, inguinal hernias, hypospadias, and club feet. The karyotype 46,XY,del(5) (pter --> p13::cen --> qter)/47,XY,+dicr(5)(:p13 --> cen::p13 --> cen), del(5)(pter --> p13::cen --> qter) was identified by banding studies and FISH analysis in the peripheral lymphocytes. One breakpoint on the del(5) maps distal to GDNF, and FISH analysis using an alpha-satellite probe suggests that the proximal breakpoint maps within the centromere. The dicentric r(5) consists of two copies of the segment deleted in the del(5), resulting in trisomy of proximal 5p (5p13-cen). The phenotype of the propositus is compared with other trisomy 5p cases and possible mechanisms for the generation of this unique chromosomal rearrangement are discussed.
TL;DR: A patient with ring chromosome 7 analyzed by both high-resolution mid-prophase G-banding and fluorescence in situ hybridization (FISH) resolving a subband deletion of 7q36.3 associated with the clinical manifestation of holoprosencephaly (HPE).
Abstract: We report on a patient with ring chromosome 7 analyzed by both high-resolution mid-prophase G-banding and fluorescence in situ hybridization (FISH) resolving a subband deletion of 7q36.3 associated with the clinical manifestation of holoprosencephaly (HPE).
TL;DR: This patient provides information regarding phenotypic variability of ring chromosome 6 and also reinforces the importance of offering amniocentesis if fetal hydrocephalus is detected as an isolated anomaly.
Abstract: A patient with ring chromosome 6/monosomy 6 mosaicism is presented. At 25 weeks' gestation, ultrasound examination demonstrated fetal hydrocephalus. Amniocentesis was performed. The fetal karyotype was 45,XY,-6/ 45,XY,-6,+f/46,XY,r(6)(p25q27). Delivery of this male infant was by Caesarean section at 37 weeks' gestation. The karyotype in peripheral blood lymphocytes was 46,XY,r(6)(p25q27) with no indications of mosaicism. The infant had hydrocephalus which required treatment with a ventriculoperitoneal shunt at 22 days of age. He had no other obvious serious congenital anomalies. By 17 months he had developed microcephaly, seizures, severe bilateral hearing loss, and global development delay. This patient provides information regarding phenotypic variability of ring chromosome 6 and also reinforces the importance of offering amniocentesis if fetal hydrocephalus is detected as an isolated anomaly.
TL;DR: The cytogenetic and clinical findings in these two individuals are discussed in relation to six previously reported cases of de novo ring chromosome 19 mosaicism.
Abstract: Ring (19) chromosomal mosaicism has been identified in a 14-month-old girl referred for cytogenetic evaluation due to microcephaly and developmental delay with autistic-like mannerisms. An analysis of her peripheral blood lymphocytes showed a 46,XX,r(19) cell line in 119/121 of cells examined. Of the two remaining cells, one had a normal female chromosome complement and the other showed loss of one of the chromosome 19 homologs. Further analysis by fluorescence in situ hybridization using an all human telomere probe showed the presence of a single hybridization signal on the r(19) chromosome. Subsequent cytogenetic characterization of cells derived from the patient's phenotypically normal mother also demonstrated the presence of a ring 19 chromosome in 4/100 cells. The remaining cells had a normal female chromosome complement. These findings represent the first reported case of familial ring 19 mosaicism. The cytogenetic and clinical findings in these two individuals are discussed in relation to six previously reported cases of de novo ring chromosome 19 mosaicism.
TL;DR: Although blood growth hormone (GH) showed normal responses to four types of provocative tests, the mean value of blood GH levels obtained at 30 min intervals for 24 h was low, indicating the existence of growth hormone neurosecretory dysfunction (GHND).
Abstract: The patient was a girl 5 years and 1 month old of markedly short stature (-3.9 SD) for her chronological age. Although her karyotype was 46, XX, r(18)(p11q23), there were no symptoms of a chromosomal deletion. Other authors have described cases with a ring autosome showing a phenotype with short stature alone as 'ring syndrome', regardless of which autosome is involved. The present case seems to fall into this category. Although blood growth hormone (GH) showed normal responses to four types of provocative tests, the mean value of blood GH levels obtained at 30 min intervals for 24 h was low, indicating the existence of growth hormone neurosecretory dysfunction (GHND).
TL;DR: A new case of ring chromosome 9 in a 36-month-old child is presented and some peculiarities, such as corpus callosum hypoplasia and epileptic seizures (infantile periodic spasms), are presented.
Abstract: A new case of ring chromosome 9 in a 36-month-old child is presented. In addition to the pathognomonic features of this rare disorder (only 21 cases reported), our patient presents some peculiarities, such as corpus callosum hypoplasia and epileptic seizures (infantile periodic spasms). We also observed a reduced level of leukocyte interferon α whose synthesis is controlled by a gene on chromosome 9 and which could be responsible for the recurrent respiratory tract infections, typical and sometimes fatal in these patients.
TL;DR: This is the first case of successful pregnancy in patient with X,Xr(X),XX mosaic Turner's syndrome, a patient with this karyotype who lacked the clinical manifestation of characteristic phenotype of Turner's Syndrome except for short stature.
Abstract: Turner's syndrome associated with an X ring chromosome, r (X), is rare and there has been no report on pregnancy in Turner's syndrome with 45,X/46,Xr (X)/46,XX mosaicism. A patient with this karyotype who lacked the clinical manifestation of characteristic phenotype of Turner's syndrome except for short stature had two pregnancies. This is the first case of successful pregnancy in patient with X,Xr(X),XX mosaic Turner's syndrome.
TL;DR: A 30-year-old women with de novo ring chromosome 12 mosaicism, 46,XX, r(12)(p13.3q24.3)/46,XX had a broad nasal bridge, micrognathia with overbite, underdeveloped breasts, mild dorsal scoliosis, clinodactyly of the fifth fingers with a single interdigital crease, symphalangism of thumbs, tapering fingers, and mild cutaneous syndactylys.
Abstract: We report on a 30-year-old woman with de novo ring chromosome 12 mosaicism, 46,XX,r(12)(p13.3q24.3)/46,XX. In addition to the clinical manifestations generally observed in {open_quotes}ring syndrome{close_quotes} cases such as growth retardation, short stature, microcephaly, and mental deficiency, she had a broad nasal bridge, micrognathia with overbite, underdeveloped breasts, mild dorsal scoliosis, clinodactyly of the fifth fingers with a single interdigital crease, symphalangism of thumbs, tapering fingers, mild cutaneous syndactyly between the second and third toes, multiple cafe-au-lait spots, sebaceous acne on the face and back, and mild dystrophic toenails. She developed a large, pedunculated uterine leiomyoma at age 28 years. To our knowledge, uterine leiomyoma in association with r(12) has not been reported previously. However, a gain of chromosome 12 and translocations involving 12q14-15 have been described. 12 refs., 5 figs., 2 tabs.
TL;DR: A prenatally detected case of ring chromosome 18 [46,XX,r(18)] in amniotic fluid cells of a fetus with an abnormal facial profile on ultrasound as the only malformation is reported, in agreement with the previous ultrasound findings.
Abstract: We report on a prenatally detected case of ring chromosome 18 [46,XX,r(18)] in amniotic fluid cells of a fetus with an abnormal facial profile on ultrasound as the only malformation. The chromosome 18 origin of the ring chromosome, of a supernumerary marker chromosome in some cells, and of micronuclei was demonstrated by fluorescent in situ hybridization with a whole chromosome 18 paint (Cambio) and 18 centromere probe L1.84. DNA investigations showed deletions of 18p as well as 18q material of r(18), which turned out to be of paternal origin. Autopsy of the fetus after termination of pregnancy at 20 weeks of gestation showed no additional malformations, in agreement with the previous ultrasound findings.
TL;DR: A somewhat dysharmonious profile is observed between the level of mental retardation and behavioural findings in the four women, while sexual development and gonadal function seemed to be normal in all four cases.
Abstract: In this paper, the authors present the case of a 24-year-old female with ring 15 chromosome syndrome. Upon examination, the patient presented with severe mental retardation, dwarfism and microcephaly, along with other minor dysmorphic stigmata. We compared this case with three other adult female cases with this chromosomal aberration. As a result, the authors observed a somewhat dysharmonious profile between the level of mental retardation and behavioural findings in the four women, while sexual development and gonadal function seemed to be normal in all four cases.
TL;DR: An 11 year old boy with short stature, learning difficulties, and no obvious facial anomalies has a ring formed by a break in the short arm at 3p23 and subsequent fusion with 3qter, which appears to be associated with the "ring syndrome" and ring instability in division rather than from any segmental aneuploidy resulting from the presence of two rearrangements.
Abstract: An 11 year old boy with short stature, learning difficulties, and no obvious facial anomalies has a ring (3)(p23q29) formed by a break in the short arm at 3p23 and subsequent fusion with 3qter. A second rearrangement involving translocation of the displaced 3p23-->pter segment to chromosome 6 at 6pter is non-reciprocal with no obvious loss of distal 6pter material. The involvement of one chromosome in two separate rearrangements is uncommon. The patient's relatively mild phenotype appears to be associated with the "ring syndrome" and ring instability in division rather than from any segmental aneuploidy resulting from the presence of the two rearrangements.
TL;DR: It is demonstrated that the formation of a ring chromosome in hematologic disorders can cause loss of genetic material not revealed by banding techniques and therefore providing further proof of the advantages of molecular cytogenetic techniques.