Showing papers on "Ring chromosome published in 2006"

Genomic profiling of bone and soft tissue tumors with supernumerary ring chromosomes using tiling resolution bacterial artificial chromosome microarrays.

Abstract: Ring chromosomes and/or giant marker chromosomes have been observed in a variety of human tumor types, but they are particularly common in a subgroup of mesenchymal tumors of low-grade or borderline malignancy. These rings and markers have been shown to contain amplified material predominantly from 12q13–15, but also sequences from other chromosomes. Such amplified sequences were mapped in detail by genome-wide array comparative genomic hybridization in ring-containing tumor samples from soft tissue (n=15) and bone (n=6), using tiling resolution microarrays, encompassing 32 433 bacterial artificial chromosome clones. The DNA copy number profiles revealed multiple amplification targets, in many cases highly discontinuous, leading to delineation of large numbers of very small amplicons. A total number of 356 (median size: 0.64 Mb) amplicons were seen in the soft tissue tumors and 90 (median size: 1.19 Mb) in the bone tumors. Notably, more than 40% of all amplicons in both soft tissue and bone tumors were mapped to chromosome 12, and at least one of the previously reported recurrent amplifications in 12q13.3–14.1 and 12q15.1, including SAS and CDK4, and MDM2, respectively, were present in 85% of the soft tissue tumors and in all of the bone tumors. Although chromosome 12 was the only chromosome displaying recurrent amplification in the bone tumors, the soft tissue tumors frequently showed recurrent amplicons mapping to other chromosomes, that is, 1p32, 1q23–24, 3p11–12, 6q24–25 and 20q11–12. Of particular interest, amplicons containing genes involved in the c-jun NH2-terminal kinase/mitogen-activated protein kinase pathway, that is, JUN in 1p32 and MAP3K7IP2 (TAB2) in 6q24–25, were found to be independently amplified in eight of 11 cases with 12q amplification, providing strong support for the notion that aberrant expression of this pathway is an important step in the dedifferentiation of liposarcomas.

Mosaic ring 20 with no detectable deletion by FISH analysis: Characteristic seizure disorder and literature review

Abstract: Ring chromosome 20 is a rare chromosome disorder characterized by a typical seizure phenotype consisting of complex partial seizures, frequent progression to generalized tonic or tonic-clonic seizures, and nocturnal frontal lobe seizures with frequent episodes of non-convulsive status epilepticus. Development may be normal or mildly delayed, followed by cognitive and behavioral decline after seizure onset. Here, we describe a patient with a typical severe seizure phenotype and a mosaic ring chromosome 20 without loss of p or q subtelomere regions or telomeric sequences. The ring had a longer telomere length than either of the telomere ends of its homologous chromosome 20 by quantitative fluorescence in situ hybridization analysis, suggesting that it might be derived from telomere–telomere fusion. The phenotypic comparison of this patient and other chromosome 20 cases that had terminal deletions of 20qter (n = 1) and 20pter (n = 7), shows that the epilepsy phenotype and electroencephalographic abnormalities are characteristic in patients with ring chromosome 20. Several hypotheses have been proposed to address the elusive mechanisms underlying the seizure disorder in ring chromosome 20. These possibilities include haploinsufficiency of two epilepsy genes CHRNA4 and KCNQ2 located at 20qter, silencing of these genes by a telomere position effect, or microdeletions or rearrangements of genetic material during the ring formation. © 2006 Wiley-Liss, Inc.

Ring chromosome 15: Characterization by array CGH

Abstract: Ring chromosome 15 [r(15)] is an uncommon finding with less than 50 patients reported. Precise genotype–phenotype correlations are problematic because of the difficulties in determining the extent of euchromatic loss, the level of mosaicism, and the influence of the timing of ascertainment. We report two discordant examples of r(15) patients. In the first case, prenatal diagnosis of a de novo r(15) was made during the second trimester: mos 46,XX,r(15)(p11.2q26)[32]/45,XX,-15[13]/47,XX,r(15)(p11.2q26)x2[3]/46,XX,dic r(15)(p11.2q26p11.2q26[1]/46,XX[2]. Postnatal follow-up revealed extremely small stature, heart defects, and developmental delay. Patient 2 was a 31-year-old short-statured female who was living independently: 46,XX,r(15)(p11q26). Both cases showed loss of the 15q subtelomeric region by fluorescence in situ hybridization (FISH). To investigate the discordance in phenotypes between the two patients, we undertook array comparative genomic hybridization (array CGH) analyses to more fully characterize the deletions associated with these otherwise structurally indistinguishable r(15) chromosomes from conventional cytogenetic analyses and fluorescence in situ hybridization (FISH) studies. By array CGH, patient 1 showed deletion of multiple contiguous clones predicting an approximately 6 Mb deletion of distal 15q. In contrast, patient 2 showed loss of just the 15q subtelomeric clone and an interstitial clone by array CGH confirming that the severity of the phenotype correlated with the size of the deletion at the molecular level. These cases illustrate the utility of array CGH characterization for determining the size of the associated deletion in ring chromosomes and for facilitating phenotype–genotype correlations.

Mosaic Turner Syndrome and Hyperinsulinaemic Hypoglycaemia

Abstract: Background. A common and well recognised feature of Turner's syndrome (partial or total monosomy X) is impaired glucose tolerance or type 2 diabetes mellitus. A small percentage of patients with Turner's syndrome have a complex mosaic karyotype with atypical clinical features and mental retardation.Methods/Patient: We report the first case of a child with a complex mosaic Turner genotype and hyperinsulinaemic hypoglycaemia responsive to diazoxide therapy.Results: Cytogenetic analysis showed four cell lines: one with 45,X; the others with an additional small ring chromosome, a small marker chromosome, and both the ring and marker chromosomes, respectively. FISH studies showed the abnormal chromosomes to originate from an X. The X inactivation locus (XIST) was present in the ring, but not in the marker chromosome.Conclusions: The recognition of hypoglycaemia in children with atypical Turner's syndrome is important as persistent hypoglycaemia may lead to brain damage in addition to the risk of mental retardation. Further studies are required to understand whether the mosaic over- or under-expression of unidentified X chromosome gene(s) in the pancreatic beta-cells leads to hyperinsulinaemic hypoglycaemia.

Hepatosplenic γδ T-cell lymphoma with ring chromosome 7, an isochromosome 7q equivalent clonal chromosomal aberration

Abstract: Hepatosplenic T-cell lymphoma is a rare, clinically aggressive lymphoma. Most cases represent a neoplasm of mature non-activated gammadelta T cells. Isochromosome 7q i(7)(q10) is thought to be the primary cytogenetic abnormality of this disease. In this paper, we describe a hepatosplenic gammadelta T-cell lymphoma case, with clonal ring chromosome 7 exemplifying an isochromosome 7q equivalent clonal aberration. A 62-year-old female patient presented with thrombocytopenia, isolated hepatosplenomegaly, and extremely high levels of LDH. Bone marrow work-up demonstrated a sinusoidal cytotoxic T-cell infiltrate with blastic features, while molecular studies verified monoclonal rearrangement for both TCR gamma and TCR delta genes. Cytogenetics revealed clonal abnormalities including ring chromosome 7, trisomy 8, and der(19), while FISH analysis detected 7q amplification with partial deletion of 7p in ring chromosome 7. To the best of our knowledge, this is the first reported T-cell lymphoma case with ring chromosome 7.

Ring chromosome 4 and Wolf-Hirschhorn syndrome (WHS) in a child with multiple anomalies.

Abstract: We report on a 16-month-old male patient with ring chromosome 4 and deletion of Wolf-Hirschhorn syndrome (WHS) region with multiple congenital anomalies including unilateral cleft lip and palate, iris coloboma, microcephaly, midgut malrotation, hypospadias, and double urethral orifices. Peripheral chromosome analysis of the patient showed 46,XY,r(4)(p16.3q35) de novo. Multicolor fluorescence in situ hybridization (FISH) study was also performed and according to multicolor banding (MCB) a r(4)(::p16.3 --> q34.3 approximately 35.1::) was found in all metaphases. Subtelomeric 4p region, subtelomeric 4q region, as well as, Wolf-Hirschhorn critical region were deleted in ring chromosome 4. Genomic microarray analysis was also performed to delineate the size of deletion. Cranial magnetic resonance imaging (MRI) showed hypoplastic corpus callosum, delayed myelinization, and frontal and occipital lobe atrophies. Both maternal and paternal chromosomal analyses were normal. We compare the phenotypic appearance of our patient with the previously reported 16 cases of ring chromosome 4 in the medical literature.

Characterization of mosaic supernumerary ring chromosomes by array-CGH: segmental aneusomy for proximal 4q in a child with tall stature and obesity.

Abstract: We report on a 6-year-old girl with developmental delay, tall stature, and obesity. G-banded chromosome analysis revealed mosaicism for one to three small de novo rings in 82% of peripheral lymphocytes. Fluorescence in situ hybridization (FISH) studies and metaphase comparative genomic hybridization (CGH) demonstrated that the rings were derived from 4q10-4q13. A higher resolution investigation was initiated using array-CGH analysis and revealed a gain of 11 adjacent clones spanning a 16 Mb region at 4q11-q13.2 and including the insulin-like growth factor binding protein 7 (IGFBP7) gene. This finding suggests that postnatal overgrowth observed in our patient might be related to a dosage effect of the IGFBP7 gene.

Dermatofibrosarcoma protuberans: report of a case with a variant ring chromosome and metastases following pregnancy.

Abstract: Background: The most frequent molecular abnormality observed in dermatofibrosarcoma protuberans (DFSP) is the formation of a supernumerary ring chromosome or translocation resulting in fusion of the gene encoding the α-chain of type 1 collagen, COL1A1 from 17q22, to the platelet-derived growth factor β-chain, PDGFB gene from 22q13. Rare cases documenting variant ring or marker chromosomes involving regions other than 17q22 and 22q13 have been reported. Further analysis in three of these cases demonstrated the presence of the COL1A1 and PDGFB genes. Methods: We report a further case of DFSP with a rare variant ring chromosome. The tumor appeared to undergo accelerated growth during pregnancy, then metastasized following pregnancy. We describe the clinical, histological, immunohistochemical, and cytogenetic features. Results: The metastatic tumor showed a variant r(17;?) chromosome. A locus-specific probe was required to demonstrate presence of the PDGFB gene within the ring, indicating cryptic molecular rearrangement between chromosomes 17 and 22, and recombination with an unknown chromosome. Conclusions: Cryptic rearrangement of chromosomes 17 and 22 should be suspected in variant ring chromosomes and translocations. Pregnancy may contribute to accelerated growth of DFSP, and delay in surgical resection should be avoided.

Ring chromosome 13 in an infant with ambiguous genitalia.

Abstract: Ring chromosome is a rare chromosomal abnormality. We report a case of ring chromosome 13 associated with ambiguous genitalia. Karyotype is the important investigation in the evaluation of a case with ambiguous genitalia and chromosomal analysis should not be limited to only presence of X and Y chromosomes.

Characterization of two supernumerary marker chromosomes in a patient with signs of Klinefelter syndrome, mild facial anomalies, and severe speech delay.

Abstract: A boy with signs of Klinefelter syndrome, mild facial dysmorphic features, and severely retarded speech development displayed a female karyotype with mosaicism for two marker chromosomes 48,XX,+mar1,+mar2[68]/47,XX,+mar1[19]/47,XX,+mar2[6]/46,XX[8]. Using chromosomal microdissection, locus-specific fluorescence in situ hybridization (FISH), and PCR with several Y-chromosome markers, the larger supernumerary marker chromosome (SMC) was characterized as a ring Y-chromosome. Detection of the SRY-region explained the male phenotype. The smaller second marker chromosome contained the pericentromeric region of chromosome 8. We suggest that the co-occurrence of a partial Y-chromosome and partial trisomy 8 explain the severe speech delay and the facial dysmorphic features.

Thai girl with ring chromosome 18 (46XX, r18).

Abstract: Chromosomal anomalies occur in 0.4% of live births. Ring chromosomes have been found for all human chromosomes and when it is replacing a normal chromosome, it results as a partial monosomy. The phenotype often overlaps that seen in comparable deletion syndromes of the same chromosomes. In the present report the authors describe the clinical manifestations of a girl with ring chromosome 18 (46XX,r18) including dysmorphic features, failure to thrive, global delay of development, hypothyroidism, atopic dermatitis, bilateral chronic otitis media, aortic regurgitation with patent foramen ovale and immunoglobulin A deficiency.

A case of mosaic supernumerary ring chromosome 15 with two copies of the segment 15p11.1-q14.

Abstract: Although supernumerary marker chromosomes derived from chromosome 15 (SMC(15)) are the most common marker chromosome in humans, ring SMC(15)s are rare. Here we report on a 16-month-old patient who has a ring SMC(15) with two copies of the segment 15p11.1-q14 region. She exhibits hypotonia, developmental delay, speech delay, microstomia, micrognathia, and other mild dysmorphic features. The ring was present in 22% of her peripheral blood lymphocyte cells. FISH study revealed that the ring was derived from chromosome 15, and had neither telomere sequence nor satellite III paracentromeric DNA. It had alpha satellite DNA, and two copies of the segment 15q11.2 to CTD 2125J1 (at 15q14, 2.2 Mbp telomeric of the common breakpoint 5). The ring-containing cells had four copies of 15p11.1-q14. The ring can be described as r(15)(::p11.1 --> q14::q14 --> p11.1::). Southern-blot analysis of the methylation pattern in the PW/AS critical region showed biparental inheritance, and the ring was maternally derived. This patient's phenotype was comparable to ring SMC(15) patients with three copies of the Prader-Willi/Angelman syndrome (PWS/AS) critical region.

Prenatal diagnosis of an unexpected interstitial 22q11.2 deletion causing truncus arteriosus and thymic hypoplasia in a ring 22 chromosome derived from a maternally inherited paracentric inversion.

Abstract: Objective To present the prenatal diagnosis of an interstitial 22q11.2 deletion involving a ring 22 chromosome associated with truncus arteriosus and a hypoplastic thymus. Case Following the sonographic diagnosis of a cystic hygroma at 12 weeks of gestation, chromosome analysis revealed a ring 22 chromosome. Results Ring chromosomes typically result in the deletion of genetic material from the distal long and short arms of the affected chromosome. The presence of an interstitial deletion in a ring chromosome is therefore unusual. FISH analysis revealed an unexpected deletion involving the TUPLE1 gene in the DiGeorge/Velocardiofacial syndrome region in 22q11.2. Maternal chromosome analysis revealed the cause of the apparent interstitial deletion, a paracentric inversion in the long arm of chromosome 22, resulting in the distal long arm of 22q being located adjacent to the centromere and the proximal end being located near the telomere. The fetus was subsequently diagnosed with truncus arteriosus and a hypoplastic thymus, consistent with DiGeorge syndrome. Conclusion The ring chromosome 22 found in the fetus appears to have been derived from a rearrangement of the mother's inverted 22, resulting in ring formation and loss of the end of the distal long arm of the inverted 22, including the TUPLE1 locus, causing DiGeorge syndrome in the fetus. The apparent interstitial deletion was actually a terminal deletion in a maternally inherited rearranged chromosome 22. Copyright © 2006 John Wiley & Sons, Ltd.

Wolf Hirshhorn syndrome in a case of ring chromosome 4: phenotype and molecular cytogenetic findings.

Abstract: Ring chromosome 4 associates concomitant loss of the telomeric 4p and 4q regions and leads to variable clinical manifestations depending on the size of the deleted chromosomal material. We report on a patient with ring chromosome 4, showing the Wolf-Hirshhorn Syndrome (WHS) phenotype and minor symptoms of distal 4q deletion syndrome; the severity of the signs of WHS masks the symptomatology of the 4q deletion syndrome. The absence of seizures despite the absence of the specific 4p16.3 region with haploinsufficiency of the LETM1 gene is striking. The double telomeric deletion due to the ring chromosome formation confirmed by FISH has been rarely described in WHS.

Primary glioblastoma with EGFR amplification and a ring chromosome 7 in a young patient.

Abstract: Glioblastoma is the most common primary tumor of the central nervous system, but the underlying genetic changes that give rise to these tumors are still poorly understood. We report a primary glioblastoma with an unusual age of presentation. The patient was a 22-year-old man with a survival of 16 months. Morphological findings showed an increase of cellularity with positive GFAP and EGFR expression, increase of proliferate index, vascular hyperplasia with glomeruloid structures and necrosis. Molecular analysis showed EGFR amplification. No mutations of the TP53 or amplification of MDM2 and CDK4 were detected. Neither homozygous deletion of the 9p21 locus genes nor aberrant methylation were found. The cytogenetic study showed a clonal karyotype. The metaphases presented, among other anomalies, a small ring chromosome and double-minutes chromosomes. Using FISH and CGH techniques, it was found that the ring chromosome was a partial trisomy of chromosome 7, and the region implicated corresponded to 7p13-q21. Partial trisomies in glioblastoma could play an important role in defining those regions where genes implicated in this tumor process may be found. We studied the possible correlation of these findings with the tumoral phenotype.

Diagnóstico Prenatal Ecográfico y Citogenético de un feto con anomalía en anillo del cromosoma 13 y demostración por Fetoscopía

Abstract: Introduction: The ring chromosome is a structural abnormality resulting from the loss of the distal portions of both arms and joining the ends to form a ring set. Ring chromosomes are uncommon and the prenatal diagnosis of such, is particularly unusual. It has been reported that the ring chromosome 13 show relatively constant and mainly associated with the deletion of the long arm. The usually consist of dysmorphic craniofacial anomalies, ocular, sternal agenesis, heart disease, digestive abnormalities, genitourinary, vertebral and limb, mental retardation and intrauterine growth. We present a female fetus of 32 weeks of gestation, who performed cytogenetic prenatal diagnosis of a ring chromosome 13 by fetoscopy showed the characteristic lesions of the injury. Case report: A review in the department of high-risk pregnancy to a woman 36 years old in his 3rd quest. With adequate prenatal care. Fetal movements were detected from the third month of pregnancy, prenatal ultrasound was performed reported as normal, but in the sixth month of gestation, ultrasound detected polyhydramnios control with hydrops fetalis, severe heart malformation (single ventricle), pleural effusion bilateral, microcephaly, depressed nasal bridge, ankylosis of upper limbs and intrauterine growth retardation severe. Amniocentesis was performed evacuated and taken sample for cytogenetic studies. Karyotype in amniocytes were performed with GTG banding techCepeda GJR, Ambriz LR, De La Fuente CBE, De La Rosa ARM, Arteaga AMG, Gonzalez DZ, Carmona MJG, Alvarez MC, Velazquez GG, Arroyo SR, Rodriguez HE, Montemayor GNG

Distinctive Phenotype in a Case of Ring Chromosome 22 with Features of 22q13.3 Deletion Syndrome

Abstract: Chromosome 22q13.3 deletion syndrome (OMIM #606232) is a well defined clinical subtelomeric deletion syndrome characterised by severe expressive language delay, moderate mental retardation and somatic overgrowth without major internal organ anomalies and minimal cranio-facial dysmorphic features. We report a case of de novo ring chromosome 22 confirmed by FISH to have deletion 22q13.3, with typical features of 22q13.3 deletion syndrome; we emphasise the importance of cytogenetic analysis in children with severe speech delay, autism, hypotonia, developmental delay, accelerated growth and minimal cranio- facial dysmorphism.

Assessment of Molecular Cytogenetic Methods for the Detection of Chromosomal Abnormalities

Abstract: Some marker chromosomes and chromosome rearrangements are difficult to identify using G-bands by Giemsa staining after trypsin treatment (G-banding) alone. Molecular cytogenetic techniques, such as spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH), can help to detect chromosomal aberrations precisely. We analyzed the karyotypes in 6 cases of multiple congenital abnormalities and 1 case of spontaneous abortion (case 2). Three cases (cases 1, 6, and 7) had marker chromosomes, and 4 cases (cases 2-5) had chromosomal rearrangements. The karyotypes in cases 1, 2, and 3 were determined using FISH with probes based on the clinical findings and family histories. Spectral karyotyping (SKY) analysis in cases 4-7 showed that this method is useful and saves time. The combination of SKY and FISH analyses defined the range of the ring chromosome in case 7. We demonstrated that a combination of G-banding, FISH, and SKY can be applied effectively to the investigation of chromosomal rearrangement and to the detection of marker chromosome origins. We suggest the use of these methods for prenatal diagnosis, in which the inherent time limitations are particularly important.

Short communication Ring chromosome 7 with amplification of 7q sequences in a pediatric case of hepatosplenic T-cell lymphoma

Abstract: Hepatosplenic T-cell lymphoma is rare, and most cases that have been reported with cytogenetic abnormalities have an isochromosome 7q with or without trisomy 8. A 7-year-old boy who had he- patomegaly and splenomegaly was diagnosed with hepatosplenic T-cell lymphoma on the basis of a bone marrow biopsy. The karyotype of the lymphoma cells at diagnosis included a ring chromo- some 7 and trisomy 8. Fluorescence in situ hybridization analysis with chromosome 7 probes dem- onstrated amplification of a 7q31 sequence in the ring chromosome. While isochromosome 7q is a common abnormality in hepatosplenic T-cell lymphoma, and other structurally abnormal chromo- somes 7 have been reported in a small number of cases, this is the first reported case of ring chro-

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Abstract: David Gisselsson Department of Clinical Genetics, University Hospital, SE-221 85 LUND, SWEDEN david.gisselsson@klingen.lu.se May 2001 Summary Many human malignant tumours exhibit abnormal chromosomal segregation at cell division. It is believed that these anomalies play a role in tumorigenesis by increasing the rate of chromosome mutations, including deletion and amplification of genes involved in cellular proliferation and/or survival. In vitro experiments have also shown that mitotic instability may be a mechanism for developing resistance to cytotoxic drugs. Abnormal mitotic mechanisms may result in numerical or structural aberrations in the daughter cells. Numerical aberrations can be caused either by the loss of chromosomes at metaphase/anaphase or by multipolar divisions associated with abnormal number or structure of centrosomes. Structural rearrangements have been associated with chromosomal breakage-fusion-bridge (BFB) cycles that can be initiated by telomeric dysfunction, giving rise to unstable dicentric or ring chromosomes. In most tumours exhibiting chromosomal instability, including highgrade malignant pancreatic, ovarian, and headand neck carcinomas, as well as osteoand soft tissue sarcomas, the two types of instability occur together. However, in some low-grade mesenchymal and neuroglial tumours, rarely showing numerical changes, BFB events involving telomeric associations and ring chromosomes dominate the mitotic process. At progression towards higher malignancy in these tumours, complex structural and numerical aberrations become more frequent. This may be explained by a process initiated by telomeric dysfunction and anaphase bridging, which, in turn, may give rise to an increased frequency of multinucleated cells through failure of cytokinesis. These cells will contain an abnormal number of centrosomes leading to multipolar mitotic figures at the next cell division. Further understanding of these events may lead to novel strategies for detection and treatment of malignancy. Introduction All malignant tumour types have been shown to contain chromosomal aberrations. The pattern of abnormalities varies greatly between malignancies, ranging from simple balanced rearrangements to complex abnormalities affecting both chromosome structure and number ( Mitelman Database of Chromosome Aberration in Cancer 2001 ). In haematological neoplasms, certain abnormalities are often strongly associated with specific diagnostic entities. Typically, these changes are reciprocal translocations such as the t(9;22) in chronic myelogenous leukaemia (Heim and Mitelman 1995). Similar genetic abnormalities are seen in some solid tumours, e.g. the 11;22 translocation in Ewing sarcomas and the inversion of proximal 10q in papillary thyroid carcinomas (Vecchio and Santoro 2000). Such