Showing papers on "Ring chromosome published in 2004"

Molecular cytogenetic characterization of ring chromosome 15 in three unrelated patients

Abstract: We report molecular cytogenetic characterization of ring chromosome 15 in three unrelated male patients with the karyotype 46,XY,r(15). One was a stillborn child with several malformations, and the other two cases showed pre- and postnatal growth retardation and developmental delay, common features for ring chromosome 15 syndrome. One of these patients also displayed clinical features resembling Prader-Willi syndrome (PWS). To delineate the extent of the deletion on chromosome 15, we have carried out fluorescence in situ hybridization (FISH) using bacterial artificial chromosomes (BACs) mapping to the distal long arm of chromosome 15. The deletion breakpoints clustered within a 4.5-6.5 Mb region proximal to the 15q telomere. Two deletions involved the same known genes, while the largest deletion observed in the stillborn child involved three additional genes, including the COUP-TFII gene, which has been suggested to play a role in heart development. The heart malformations, which are observed in this patient, are thus likely to be due to hemizygosity/haploinsufficiency of the COUP-TFII gene. In all three patients, the insulin-like growth factor I receptor gene (IGF1R) gene was deleted supporting the association between IGF1R and growth retardation seen in ring chromosome 15 syndrome.

Amplification of chromosome 1 sequences in lipomatous tumors and other sarcomas.

Abstract: Amplifications and gains involving 1q are common abnormalities in solid tumors. Recently, an amplicon originating from 1q21-23, containing the candidate oncogenes COAS1, COAS2 and COAS3 (Chromosome One Amplified Sequence) was identified. The presence, distribution and copy number level of extra COAS sequences were investigated in 48 bone and soft tissue tumor (BSTT) samples using metaphase FISH analysis. Amplification was seen in 27/48 (56%) samples. With few exceptions, all 3 genes were involved, but on average COAS2 exhibited higher copy numbers. The presence of extra COAS signals, irrespective of copy numbers, was found at similar frequencies in different histologic tumor subtypes. However, medium or high level amplification was common in lipomatous tumors but rare in other, nonlipomatous tumors (9/21 vs. 2/27 samples). The most common localization of extra COAS signals in lipomatous tumors was in supernumerary ring and giant marker chromosomes. Among nonlipomatous tumors, the distribution of extra COAS genes was more disperse, being located in various unidentified chromosomal structures, including double minutes, and only rarely in ring chromosomes. Because MDM2 is known to be amplified frequently in BSTTs, and in particular in atypical lipomatous tumors, cases with extra copies of COAS were studied also with an MDM2 probe. Twelve out of 18 lipomatous tumors had extra copies of both COAS and MDM2, and the 2 genes were found to be coamplified and interspersed exclusively in ring and giant marker chromosomes. Also 12 out of 18 nonlipomatous tumors exhibited simultaneous gain of COAS and MDM2, but colocalization in the same chromosome was less frequent. The role of the frequent coamplification of COAS, or some other yet unknown gene in the 1q21-23 region, and MDM2 remains to be elucidated.

Identification and Molecular Characterization of a de novo Supernumerary Ring Chromosome 18 in a Patient with Klippel‐Trenaunay Syndrome

Abstract: Summary Klippel-Trenaunay syndrome (KTS) is a congenital vascular disorder comprised of capillary, venous and lymphatic malformations associated with overgrowth of the affected tissues. In this study, we report the identification of a de novo supernumerary ring chromosome in a patient with mild mental retardation, long tapering fingers, elongated, thin feet and Klippel-Trenaunay syndrome (KTS). The ring marker chromosome was found to be mosaic, present in 24% of cells, and was later shown to be derived from chromosome 18, r(18). Fluorescence in situ hybridization (FISH) was used to define the breakpoints involved in the formation of r(18). The chromosome 18p breakpoint was localized between the markers WI-9619 and D18S1150, which is less than 10 cM to the centromere. The 18q breakpoint was localized between the centromere and BAC clone 666n19, which is a region of less than 40 kb. These data suggest that the r(18) mostly originated from 18p, with an estimated size of less than 10 cM. These studies identify and characterize a new marker chromosome 18, provide insights into the understanding of the relationships between the clinical phenotypes and marker chromosomes, and establish a framework for finding a potential vascular and/or overgrowth gene located on chromosome 18.

Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis 2

Abstract: Neurofibromatosis type 2 (NF2) is an autosomal dominant condition characterised by vestibular schwannomas, schwannomas of other cranial nerves, meningiomas, and other low grade brain malignancies.1 The severity of NF2 is variable, with some patients having early onset disease and more rapidly growing tumours that occur in greater numbers. The NF2 gene is on chromosome 22q12.2,3 The protein product (termed merlin or schwannomin) is a cell cytoskeleton associating protein. Genotype−phenotype correlations have been demonstrated, with missense mutations and large deletions causing mild disease, and nonsense or frameshift mutations causing severe disease.4,5 The current mutation screening techniques of single strand conformation polymorphism analysis (SSCP), protein truncation test, and denaturing gradient gel electrophoresis detect 33–65% of mutations, although adding a deletion strategy increases the proportion to 80%.6 However, deletion testing and chromosome analysis are rarely reported in studies of NF2 mutations. In this study, we present five NF2 patients for whom chromosome analysis, usually following routine molecular screening, revealed the underlying genetic aberration. ### Case 1 A 20 year old female was referred with a large diffuse goitre commencing early in puberty, moderate learning difficulties, and bilateral sensorineural hearing loss, which resembles the phenotype of Pendred’s syndrome. She was born after a normal pregnancy and delivery. Her physical and mental development during early infancy was not remarkable, but developmental delay became apparent in the second year of life. Growth parameters were within the normal range. She began to walk at the age of 3 years. Six months later, audiometric tests showed no hearing impairment although chronic otitis media was diagnosed on one side. According to the parents, her communication had been improving with age, but her speech remained dysarthric and her articulation was very poor. In primary school, she had sub-average grades in all subjects. Her affect was good and …

Short communication Myxoinflammatory fibroblastic sarcoma with complex supernumerary ring chromosomes composed of chromosome 3 segments

Abstract: Myxoinflammatory fibroblastic sarcoma is a rare, recently described, and distinctive low-grade tumor of soft tissue. To our knowledge, there is only one previous report on the cytogenetics of this tumor. That case showed complex structural abnormalities, including a reciprocal translocation between chromosomes 1 and 10 (t(1;10)(p22;q24)) with loss of chromosomes 3 and 13. We describe here a second case showing supernumerary ring chromosomes, and a derivative chromosome 13, with additional material on the short arm. We conclude that the presence of chromosomal abnormalit- ies supports the neoplastic nature of this tumor and aids in its diagnosis. Furthermore, we also postulate that the finding of ring chromosomes, which have been identified in other low-grade soft- tissue tumors, may have important prognostic implications regarding the aggressiveness of this

FOXC1 gene deletion is associated with eye anomalies in ring chromosome 6.

Abstract: We report a case of ring chromosome 6 presenting with growth and mental retardation, cerebral dysgenesis, eye malformations, mixed hearing loss, and abnormal physical features. Fluorescent in situ hybridization (FISH) and microsatellite genotyping demonstrated segmental deletions of less than 6 Mb on 6p and 1-2 Mb on 6q. The primary karyotype is designated as 46,XY,r(6)(p25q27).ish r(6)(p25.1q27)(D6S344-, FOXC1-, D6S1574+, D6S281-, D6S297+). Secondary structural and numerical variants of the ring 6 were observed in 16% of the cells analyzed. Intragenic genotyping revealed deletion of the paternal FOXC1 gene, haploinsufficiency of which has been reported to cause eye anterior chamber developmental defects. Accordingly, we propose that our patient's ophthalmologic abnormalities result from haploinsufficiency of the transcription factor FOXC1. We present clinical and cytogenetic summaries on 23 reported cases of ring 6 and categorize them into mild, moderate, and severely affected groups. Further phenotype comparisons between cases with ring 6 and cases with only 6p or 6q terminal deletions suggest that genes important for hearing, vision, and central nervous system development remain to be identified in chromosome 6 terminal regions. Molecular definition of the fusion points and tissue mosaicism studies are necessary to better understand the genotype-phenotype correlation of ring 6. We recommend ophthalmology, audiology, cardiology, and central nervous system examinations be part of the routine evaluation for children with a ring chromosome 6.

Inherited ring chromosome 8 without loss of subtelomeric sequences.

Abstract: We report the first case of inherited ring chromosome 8 syndrome without loss of subtelomeric sequences The proband is a 6 1/2-year-old boy with short stature, microcephaly, mild mental retardation, and behavioral problems including hyperactivity and attention deficit His mother presented the same physical features but intelligence was normal Family history also revealed an uncle and a grandmother, with short stature and microcephaly Moderate mental retardation was reported in the uncle Karyotypes and fluorescence in situ hybridization (FISH) analyses were performed on peripheral blood lymphocytes for both child and mother The child’s karyotype was reported as 46,XY,r(8)(p23q243)[24]/45,XY,–8[2] and the mother’s karyotype 46,XX,r(8)(p23q243)[22]/45,XX,–8[2]/47,XX,r(8)(p23q243), +r(8)(p23q243)[1] FISH studies showed no deletion of subtelomeric sequences for both child and mother indicating that no or little chromosomal euchromatic material has been deleted These findings indicate that ring chromosome 8 without loss of subtelomeric sequences can be inherited and that carriers in a same family present with cognitive function ranging from mild mental retardation to normal intelligence

Transmission of ring chromosome 13 from a mother to daughter with both having a 46,XX, r(13)(p13q34) karyotype.

Abstract: Ring chromosomes are thought to be the result of breakage in both arms of a chromosome, with fusion of the points of fracture and loss of the distal fragments Another mechanism of ring formation is believed to be the simple fusion of chromosome ends with preservation of telomeric and subtelomeric sequences Ring chromosome 13 was first described in 1968 and its incidence estimated at 1 in 58,000 live births Severe phenotypes associated with large deletions of 13q have been described as "ring chromosome 13 syndrome" Features of the "ring chromosome 13 syndrome" include mental retardation (often severe), growth retardation, microcephaly, facial dysmorphism, and hand, foot or toe abnormalities We report on a case of a mother and daughter with r(13) and mild phenotypes Our patient, IA, had chromosome analysis performed at about 4(1/2) years of age due to some developmental delay This revealed 46,XX, r(13)(p13q34) karyotype with no loss of any chromosomal band Her mother, EA, was subsequently found to have the same ring 13 IA's maternal grandmother had a normal karyotype while her maternal grandfather was unavailable for testing Fluorescence in situ hybridization (FISH) analysis showed loss of a specific subtelomeric 13q region in r(13) in the mother Clinically, IA had macular hyperpigmentation on the chin and mild delay in speech and fine motor skills EA, 22 years of age, had mild short stature and borderline mental retardation To our knowledge, this is the first report of a case of familial transmission of r(13) We compare phenotypes of our cases with those from other reported cases of r(13) and discuss the possible mechanism of formation of this ring chromosome

Characterization of the phenotype and definition of the deletion in a new patient with ring chromosome 22.

Abstract: The clinical phenotype of patients with ring chromosome 22 includes mental retardation with severe language impairment, hypotonia, and dysmorphic facial features. In recent years an increasing number of patients with microscopic as well as cryptic terminal deletion involving band 22q13 have been described and their phenotype shows clinical features overlapping with patients with ring chromosome 22. Loss of DNA in the 22q13.3 region may lead to a clinically recognizable syndrome named “22q13.3 deletion syndrome.” We report a patient with a ring chromosome 22 who has hypotonia, profound mental retardation, language impairment, dysmorphic features, and behavioral disorders. To check if the critical region responsible for “22q13.3 deletion syndrome” was absent in this ring, a fluorescent in situ hybridization (FISH) analysis using a probe corresponding to the ARSA locus was performed. In our patient, only one ARSA signal could be detected, indicating that the deletion encompassed the critical 22q13.3 region. A more detailed analysis of the deletion extent then was performed using a panel of fluorescent probes located within 22q13. These experiments allowed the identification of the breakpoint between CTA-299D3 and RP5-925J7 probe, located in 22q13.32. Deletion extent could be estimated to be about 2.5 Mb, and this larger deletion may explain the severity of clinical features observed in our patient. © 2004 Wiley-Liss, Inc.

Atypical lipomatous tumor: molecular characterization.

Abstract: Purpose of reviewAtypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLs) are one of the more frequent mesenchymal neoplasms and are characterized by specific chromosome aberrations: supernumerary chromosome or giant marker chromosome or both. Extra copies of known oncogenes such as MD

Supernumerary ring chromosome 8: Clinical and molecular cytogenetic characterization in a case report

Abstract: We report on a 3-year-old male with developmental delay, autistic behavior, and minor abnormalities consistent with trisomy 8 syndrome whose cytogenetic analysis revealed mosaicism for a supernumerary ring chromosome (SRC). Fluorescence in situ hybridization (FISH) studies, using centromeric and yeast artificial chromosome (YAC) probes, were performed to characterize further the supernumerary chromosome. The ring origin has been detected from the short arm of chromosome 8, resulting in r(8)(p10p23.1). Moreover, uniparental disomy (UPD) using microsatellite analysis was excluded. To our knowledge a total of 25 cases, confirmed by FISH, have been reported with either supernumerary marker or ring chromosome 8. We present a detailed clinical and molecular cytogenetic characterization of this additional case in order to better define the genotype-phenotype correlation.

Dilated ascending aorta in a child with ring chromosome 21 syndrome

Abstract: Ring chromosome 21 syndrome is a rare condition with a well-characterized phenotype. Affected individuals have recognizable dysmorphic features, developmental delays, growth retardation, and a predisposition for congenital malformations involving the neurologic, craniofacial, digestive, genitourinary, skeletal, and hematologic systems. Structural cardiac anomalies have also been described, but dilated ascending aorta has not been previously reported in association with ring 21 (r(21)). Although rarely seen in this syndrome, the presence of ectopia lentis, abdominal herniae, and dilated ascending aorta suggest an underlying connective tissue disorder. A possible explanation is haploinsufficiency of the COL6A1, COL6A2, and/or COL18A genes located on the distal portion of chromosome 21q, which are lost when the ring chromosome is formed. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html. © 2004 Wiley-Liss, Inc.

A patient with Prader-Willi syndrome and a supernumerary marker chromosome r(15)(q11.1-13p11.1)pat and maternal heterodisomy.

Abstract: We report on a Prader-Willi patient with a de novo supernumerary marker chromosome (SMC) in 16% of the cells. The SMC was a ring chromosome and it included the PWS/AS critical region as was demonstrated by FISH. Segregation analysis indicated that the SMC originated from a paternal chromosome 15 and the two normal chromosomes 15 of the patients were of the maternal homologues. Namely, the patient had maternal heterodisomy in 85% of the cells and triplication of the PWS/AS region in 15% of the cells. The Prader-Willi features were the result of the low mosaicism of the SMC. The evolution of the maternal heterodisomy and the SMC were two unrelated events, the occurrence of both events in the same embryo rescued it from lethality.

Ring chromosome 18q and jumping translocation 18p in an adult male with hypergonadotrophic hypogonadism.

Abstract: Constitutional jumping translocations (JT) are rare, especially in phenotypically normal individuals. We report on an adult male with partial hypogonadism as the sole phenotypic abnormality with an unusual chromosome abnormality. In this patient, centric fission of chromosome 18 lead to formation of a ring 18q chromosome, while 18p formed a JT through centromere-telomere fusion with chromosome 8q (66%) or 20q (13%). In 21% of cells, the 18p fragment was missing. Fluorescent in situ hybridization revealed the presence of interstitial telomeres at the junction site of the fusion and unequal distribution of the alphoid sequences through the centric fission, leaving a small, yet functional centromere within the ring. We discuss the phenotype of the patient in light of this unusual karyotype.

Somatic mosaicism of chromosome 7 in a highly proliferating melanocytic congenital naevus in a ring chromosome 7 patient.

Abstract: Ring chromosome 7 is a rare but well documented chromosomal aberration in man So far at least 14 cases have been reported in the literature showing a variable but distinct pattern of phenotypic characteristics in affected individuals Besides others, skin findings as pigmented naevi are especially frequent Loss of chromosomal material from the terminal chromosome arms in the structurally abnormal ring chromosome 7 as well as somatic mosaicism with loss or gain of chromosome 7 has been suggested to be responsible for the clinical symptoms We now report another case of a ring chromosome 7 in a 14-year-old boy with multiple remarkable congenital naevi, where we could demonstrate for the first time somatic mosaicism showing significant gain of chromosome 7 within a highly proliferating melanocytic congenital naevus (MCN)

A case of ring chromosome 22 with deletion of the 22q13.3 region associated with agenesis of the corpus callosum, fornix and septum pellucidum.

Abstract: We report a 16-week-gestation foetus obtained by voluntary abortion after prenatal diagnosis, in which a ring chromosome 22 was observed with deletion of the 22q13.3 region. A prenatal study of the amniotic fluid by standard chromosome technique with G bands and FISH (fluorescence in situ hybridisation) was performed. After the abortion, the anatomopathological study of the obtained foetus was carried out. Morphological and histological analysis of the foetus did not reveal severe physical abnormalities, although alterations of the nervous system were observed consisting of corpus callosum, fornix and septum pellucidum agenesia. It could be that the genes in this region that were involved in the development of the central nervous system were responsible for the alterations found in the morphological study. The wide range of manifestations observed in patients with this cytogenetic alteration is probably due to size differences in the deleted region.

Ring Chromosome 18: Clinical, Cytogenetic and Molecular Genetic Studies on Four Patients

Abstract: Ring chromosomes are a rare chromosomal aberration but have meanwhile been reported for nearly all human chromosomes. We describe four de novo carriers (1 boy and 3 girls) of ring chromosome 18 (r(18)): while three patients had a non-mosaic 46,r(18) karyotype, the fourth was a mosaic: mos 46,XX,r(18)/46,XX,der(18). Phenotypically, the boy showed only minor anomalies, but the female probands presented several clinical features, among them microcephaly, a moderate to severe muscular hypotonia, psychomotoric retardation and short stature. Major malformations were heart defects, cleft lip and palate and atresia of the external auditory canal. In one girl with very short stature, we found a hypothalamic growth hormone deficiency. By investigating the children over 2,5 years it could be demonstrated that the ring chromosomes were passed regularly through mitosis. The parental origin of the ring was determined in three cases indicating a postzygotic mitotic error.

Clinical findings and cytogenetic analysis of small supernumerary ring chromosomes 7: report of two new cases

Abstract: Two new patients, mosaic for a small supernumerary ring chromosome 7 are described. There are only seven published reported concerning supernumerary ring chromosome 7 and we reviewed the previously reported cases in an attempt to establish genotype-phenotype correlations, which are particularly important for genetic counselling and clinical genetics. Our first case was a 20 months old girl who was referred for a mild motor developmental delay, an asymmetric facial appearance, a plagiocephaly and a short nose with anteverted nostrils. Our second case was a 9 years old boy who was referred for a IQ at the lower end of the normal range (? 80), obesity, hyperactivity and some dysmorphic features including hypertelorism and down slanting palpebral fissures. In both cases, chromosome analysis after G and R banding and FISH showed a small ring chromosome 7 in respectively 76% and 50% of consecutively scored metaphases. Both ring chromosomes were labelled by FISH using the Williams Syndrome locus probe (Elastin Gene D7S486). Comparison between these two cases and previously published cases allowed to delineate frequent clinical findings. A mild mental retardation was found in the majority of patients. which is an important data for genetic counselling.

Sister chromatid exchanges in ring chromosomes following X-irradiation of human lymphocytes.

Abstract: Purpose: To examine whether X‐rays induce sister chromatid exchanges (SCE).Materials and methods: Peripheral lymphocytes irradiated in vitro or in vivo were cultured and treated with okadaic acid to generate premature chromosome condensation (PCC). When identical spreads were analysed using conventional Giemsa staining and pan‐centromeric fluorescence in situ hybridization painting, ring chromosomes were observed.Results: In PCC preparations, cells in the late G2 phase and late M phase were observed. In late M phase cells, 17–20% of ring chromosomes lacked one chromatid (single‐chromatid ring), irrespective of dose. Both the distribution patterns of centromeres in rings and intercentromere distances in dicentric rings indicate that a considerable number of single‐chromatid rings might be formed by SCE occurring in a chromosome‐type ring, thereby joining strands of two rings, followed by a transformation into one ring. These single‐chromatid rings were less stable in vivo than chromosome‐type rings.Conclus...

Distinct MDM2 and P14ARF expression and centrosome amplification in well‐differentiated liposarcomas

Abstract: Well-differentiated liposarcomas (WDLs) are common soft-tissue tumors in adults. They are characterized by large marker chromosomes and/or ring chromosomes containing 12q-derived sequences in which MDM2 is consistently amplified. WDLs are subdivided into two subtypes according to their karyotype. Type D cells exhibit a near-diploid karyotype, with very few or no chromosome changes. Type H cells exhibit a near-tetraploid karyotype and many structural changes. Expression of P14ARF, MDM2, and TP53 proteins was assayed in the two WDL subtypes to establish whether distinct expression profiles correlated with cell ploidy. Although a transcriptionally functional TP53 was present in most tumors independent of their karyotype, type H cells were characterized by high levels of P14ARF and MDM2 proteins. Although amplified within similar chromosome markers in type D tumors, MDM2 did not appear to be overexpressed. In addition, it was present as a C-terminal truncated protein, indicative of alternatively spliced variants of MDM2 mRNA. As the existence of karyotypically distinct tumors could result from alterations of the mitotic machinery, we investigated the centrosome behavior in the two WDL subtypes. Centrosome amplification occurred in WDL tumors types H and D independent of their ploidy status. Moreover, no functional centrosome difference was found between the two tumor subtypes.

Malignant refractory epilepsy in identical twins mosaic for a supernumerary ring chromosome 19.

Abstract: We report identical twins with supernumerary ring chromosome 19 mosaicism, who had severe refractory epilepsy at an early age. The epilepsy was dominated largely by severe life-threatening tonic seizures. Both twins died, likely as a consequence of their severe epilepsy. They displayed no dysmorphic features. Eight cases of ring chromosome 19 have been reported in the literature, all to our knowledge without epilepsy. The clinical picture of these twins emphasizes the importance of carrying out a karyotype study on patients with early-onset epilepsy even in the absence of dysmorphic features.

Turner syndrome female with a small ring X chromosome lacking the XIST, an unexpectedly mild phenotype and an atypical association with alopecia universalis

Abstract: Rearranged X chromosome in Turner syndrome (TS) are generally well tolerated but in cases of ring X chromosomes and of X/autosome translocations the incidence of mental retardation and other congenital abnormalities can be significantly higher. These abnormal phenotypes can be ascribed to failed or partial X inactivation. Here, we report a 10-year-old female who was referred for a cytogenetic analysis because she developed an alopecia universalis. The patient, of normal intelligence, had been found to have traits of TS, especially short stature. A first cytogenetic analysis showed a no mosaic 45,X karyotype. Since, the risk of developing gonadoblastoma in TS patients with mosaicism for a Y derivative chromosome and because association of alopecia universalis and TS is uncommon, fluorescence in situ hybridization (FISH) was performed to search for a second cell population. Our patient was found to have a mosaic 45,X/46,X,+r. FISH analysis using sex chromosome probes permitted us to identify the very small marker as a ring X chromosome, detected in 90% of cells. The ring appeared to be formed almost totally of alphoid sequences with breakpoints in the juxtacentromeric region. The r(X) does not include the XIST locus and may, therefore, not be subject to X-inactivation. Unexpectedly mild phenotype in our patient and its association with alopecia universalis will be discussed.

Mosaic ring 12p and total anomalous pulmonary venous return

Abstract: An infant born with total anomalous pulmonary venous return (TAPVR) was found to have an extra chromosome present as a small ring. Spectral karyotyping and FISH analysis identified the material as a duplication involving the short arm of chromosome 12. Previous cases describing a variety of cytogenetic abnormalities that have been associated with TAPVR are reviewed along with prior cases of duplication 12p with their associated findings. We believe ours is the first case to report the occurrence of mosaic ring 12p and its association with TAPVR.

Molecular cytogenetic characterization shows higher genetic homogeneity in conventional renal cell carcinoma compared to other kidney cancers.

Abstract: In this study seven primary kidney tumors out of 13 were cytogenetically characterized by comparative genomic hybridization (CGH) on the surgical specimens as well as by spectral karyotyping (SKY) analysis after short-term culturing. In two of the seven cases only a normal karyotype was identified. Non-clonal aberrations were observed in four of the seven cases. Overall numerical alterations were more frequent than structural changes. The two structural alterations identified constituted of a deletion of the short arm of chromosome 3 in a conventional renal cell carcinoma (RCC), and a ring chromosome derived from chromosome 8 in a papillary RCC. By CGH gains of copy number were revealed on chromosomes 3, 5, 7, 8q, and 20, while the losses encompassed 3p and 17p. In the papillary RCCs only gains were found. Comparison between SKY and CGH data suggests that the conventional RCCs are genetically more homogeneous than the other types of kidney cancer. In the two papillary RCCs, trisomies of chromosomes 7 and 17 were typical findings. In the transitional cell carcinoma different findings by CGH and SKY would suggest that these tumors constitute a heterogeneous population of tumor cells which could represent different steps of somatic evolution of tumors.

Prenatal diagnosis of ring chromosome 6 in a fetus with cerebellar hypoplasia and partial agenesis of corpus callosum: case report and review of the literature

Abstract: Ring chromosome 6 (RC6) is a rare constitutional abnormality, with variable material loss, leading to a variable clinical phenotype: minimal physical anomalies and mild psychomotor retardation to severe physical and mental defects. Among the 22 published cases, only five have been prenatally detected. We describe here a RC6 prenatally diagnosed. Ultrasound follow-up showed growth retardation and cerebellar hypoplasia. Magnetic resonance imaging (MRI) confirmed this, but showed a partial corpus callosum agenesis, leading to amniocentesis and revealing the chromosomal abnormality. Imaging features were correlated with autopsy findings.

Retained heterodisomy for chromosome 12 in atypical lipomatous tumors: implications for ring chromosome formation.

Abstract: Atypical lipomatous tumor (ALT) is an intermediate malignant mesenchymal tumor that is characterized by supernumerary ring chromosomes and/or giant rod-shaped marker chromosomes (RGMC) Fluorescence in situ hybridization ( FISH) and molecular genetic analyses have disclosed that the RGMCs always contain amplified sequences from the long arm of chromosome 12 Typically, RGMCs are the sole clonal changes and so far no deletions or other morphologic aberrations of the two normal-appearing chromosomes 12 that invariably are present have been detected The mechanisms behind the formation of the RGMCs are unknown, but it could be hypothesized that RGMC formation is preceded by trisomy 12 or, alternatively, that ring formation of one chromosome 12 is followed by duplication of the remaining homolog The latter scenario would always result in isodisomy for the two normal-appearing chromosomes 12, whereas the former would yield isodisomy in one-third of the cases In order to investigate these possible mechanisms behind ring formation, we studied polymorphic loci on chromosome 12 in 14 cases of ALT showing one or more supernumerary ring chromosomes and few or no other clonal aberrations at cytogenetic analysis The molecular genetic analyses showed that the tumor cells always retained both parental copies of chromosome 12, thus refuting the trisomy 12 and duplication hypotheses Copyright (C) 2004 S Karger AG, Basel

Clinical and molecular cytogenetic studies in a case with partial trisomy 12p due to a de novo supernumerary ring chromosome.

Abstract: Clinical and molecular cytogenetic studies in a case with partial trisomy 12p due to a de novo supernumerary ring chromosome: We report on a girl with a mosaic karyotype containing a supernumerary ring chromosome Fluorescence in situ hybridization (FISH) studies showed that this marker chromosome was derived from chromosome 12, resulting in partial trisomy 12p131-->12q11 The girl showed developmental delay, cerebral visual impairment, obesity and mild dysmorphic features Her clinical data at 6 months, 3 years, and 6 years of age were compared with the clinical data on other trisomy 12p patients

[Turner's syndrome in mother and daughter].

Abstract: A girl with Turner's syndrome due to a 45,X mosaicism and a ring chromosome was born to a 29-year-old mother with a non-mosaic 45,X in her blood lymphocytes. Cytogenetic investigation revealed that the ring chromosome of the daughter included almost the entire X chromosome with the exception of the uppermost part of the short arm. In the literature, girls with Turner's syndrome are said to have functional ovarian tissue and pregnancies in women with Turner's syndrome after oocyte donation and intracytoplasmatic sperm injection (ICSI) are no longer exceptional. However, since ovarian failure occurs relatively early during adolescence, cryopreservation of ovarian tissue should be considered as soon as the girl or her parents are able to make the necessary decisions. On the other hand, beside risks for congenital anomalies in the newborn, the risks of pregnancies in Turner's syndrome should not be neglected, notably premature delivery due to disproportion between the pelvis and the foetus and aortic dissection in the pregnant woman.