Showing papers on "Ring chromosome published in 2001"

Cytogenetical Dose Estimation for 3 Severely Exposed Patients in the JCO Criticality Accident in Tokai-mura

Abstract: A dose estimation by chromosome analysis was performed on the 3 severely exposed patients in the Tokai-mura criticality accident. Drastically reduced lymphocyte counts suggested that the whole-body dose of radiation which they had been exposed to was unprecedentedly high. Because the number of lymphocytes in the white blood cells in two patients was very low, we could not culture and harvest cells by the conventional method. To collect the number of lymphocytes necessary for chromosome preparation, we processed blood samples by a modified method, called the high-yield chromosome preparation method. With this technique, we could culture and harvest cells, and then make air-dried chromosome slides. We applied a new dose-estimation method involving an artificially induced prematurely condensed ring chromosome, the PCC-ring method, to estimate an unusually high dose with a short time. The estimated doses by the PCC-ring method were in fairly good accordance with those by the conventional dicentric and ring chromosome (Dic+R) method. The biologically estimated dose was comparable with that estimated by a physical method. As far as we know, the estimated dose of the most severely exposed patient in the present study is the highest recorded among that chromosome analyses have been able to estimate in humans.

Detailed characterization of 12 supernumerary ring chromosomes using micro-FISH and search for uniparental disomy.

Abstract: Twelve patients with varying degrees of mosaicism for a supernumerary ring chromosome were studied. The ring chromosomes were characterized using microdissection in combination with degenerate nucleotide-primed polymerase chain reaction (PCR) and reverse painting (micro-FISH). This method made it possible to determine the chromosomal origin of the ring chromosomes in detail, and thus to compare the phenotypes of similar cases. Eleven of the marker chromosomes were derived from the most proximal part of 1p, 3p, 3q, 5p, 7q, 8p, 8q, 9p, 10p and 20p. One marker chromosome had a complex origin, including the proximal and the most distal part of 20q. Eight of the families were also investigated for uniparental disomy (UPD) using microsatellite analysis. One case with maternal UPD 9 was found in a child with a ring chromosome derived from chromosome 9, r(9)(p10p12). © 2001 Wiley-Liss. Inc.

De novo terminal deletion of chromosome 15q26.1 characterised by comparative genomic hybridisation and FISH with locus specific probes

Abstract: Editor—Reports of patients with terminal de novo deletions of chromosome 15q26 are rare. Excluding cases of ring chromosome 15 formation with different sized deleted chromosomal segments, only seven cases with solely distal deletions of 15q have been published.1-7 All other cases resulted from unbalanced reciprocal translocations involving different chromosomes and are therefore not comparable with de novo terminal deletions as described in our case. With two exceptions, all de novo cases had interstitial deletions between chromosomal bands 15q21-q25. Only the patients described by Roback et al 5 and Siebler et al 6 had terminal deletions of 15q26.1. The deletions in these patients were not investigated by FISH, but molecular genetic techniques showed the loss of one copy of the insulin-like growth factor 1 receptor gene. IGF1R is a tyrosine kinase containing transmembrane protein that plays an important role in cell growth control. It has been assumed that monozygosity for this gene, which maps to distal 15q26, will directly disturb this pathway and inhibit normal growth of patients.8 Today, in addition to classical cytogenetic banding methods, FISH techniques including comparative genomic hybridisation (CGH) can be used to provide a powerful tool to characterise chromosomal aberrations. In this study, we present the molecular cytogenetic findings and the detailed clinical phenotype of a girl with deletion 15q26.1 and compare these with other published cases. Our patient described here is, to the best of our knowledge, the second patient with a de novo terminal deletion at 15q26.1 and the first one well characterised by molecular cytogenetic techniques. The female infant was the first child of healthy, unrelated parents. An ultrasound examination at 15 weeks of gestation showed intrauterine growth retardation. At 39 weeks of gestation a caesarean section became necessary because of fetal heart rate deceleration. The Apgar scores were …

Chromosome imbalances associated with epilepsy

Abstract: Epilepsy is among the most frequent findings in many, especially autosomal, chromosome aberrations. Its incidence, however, is very variable, and there are very few aberrations in which epilepsy is a constant finding. Even siblings and monozygotic twins with the same aberration are often discordant for seizure disorders. Similar observations can be made for congenital (major) malformations in chromosome aberrations. The common explanation is that in these instances epilepsy is not caused by the action of a single gene in single or triple dose, but is influenced by the combined action of a number of genes within and outside of the aneuploid segment. The situation is comparable to a polygenic model of inheritance. Gene mutations associated with epilepsy are known, to date, only for two disorders: the lissencephaly 1 gene in Miller-Dieker syndrome and mutations in the UBE3A gene in Angelman syndrome. Chromosome aberrations in which epilepsy is a major and consistent finding include Angelman syndrome due to loss of the maternal 15q11.2-q12 segment, tetrasomy of the maternal segment 15pter-q13 due to an additional inv dup chromosome, Miller-Dieker syndrome due to deletion of the 17p13.3 segment including the lissencephaly1 gene, ring chromosome 20, and Wolf-Hirschhorn syndrome due to deletion of at least the 4p16.3 segment.

Ring X and other structural X chromosome abnormalities: X inactivation and phenotype

Abstract: Patients who carry a structural abnormality of the X chromosome are a fascinating group who have provided opportunities to evaluate genotype/phenotype correlation in relation to X chromosome content and inactivation. Turner syndrome (TS) is most commonly associated with a 45,X karyotype and presents with an array of phenotypes, the main ones being poor viability in utero, ovarian failure and infertility, short stature, lymphedema, and other congenital malformations but usually not mental retardation. In some TS patients the karyotype shows both a normal X and a structurally rearranged X chromosome. These structural abnormalities, which include deletions, duplications, inversions, translocations, and rings, are associated with chromosome breaks and significant imbalance of gene content of the X chromosome. However, such abnormalities are generally well tolerated because of the preferential inactivation of the abnormal X, which can restore, at least in part, a balanced genetic makeup. This beneficial effect of X inactivation results in a mild phenotype in most patients with structural abnormalities of the X, similar to that found in TS patients with a 45,X karyotype. However, in cases of ring X chromosomes and of X/autosome translocations the incidence of mental retardation and other congenital abnormalities can be significantly higher than in TS. These abnormal phenotypes can be ascribed to failed or partial X inactivation and/or incomplete selection in favor of cells with normal balance of gene expression. In this article, we present phenotype/genotype correlation in female patients with structural abnormalities of the X and address the role of X inactivation and cell selection in the phenotypic findings. Our review emphasizes a subset of rare patients with ring X chromosomes who have provided evidence of a direct role for X inactivation in determining phenotypes.

Clinical and molecular‐cytogenetic studies in seven patients with ring chromosome 18

Abstract: We report the results of detailed clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Classical cytogenetics and fluorescence in situ hybridization (FISH) analysis with the chromosome 18 painting probe identified five non-mosaic and two complex mosaic 46,XX,dup(18)(p11.2)/47,XX,dup(18)(p11.2),+r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup(18)(p11.32),+r(18) cases. FISH analysis was performed for precise characterization of the chromosome 18 breakpoints using chromosome 18-specific short-arm paint, centromeric, subtelomeric, and a panel of fifteen Alu- and DOP-PCR YAC probes. The breakpoints were assessed with an average resolution of approximately 2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions ranging from 18q21.2 to 18q22.3 ( approximately 35 and 9 Mb, respectively) were found, whereas only in four cases could the loss of 18p material be demonstrated. In two cases the dup(18) chromosomes were identified as inv dup(18)(qter-->p11.32::q21.3-->qter) and inv dup(18)(qter-->p11.32::p11.32-->p11.1: :q21.3-->qter)pat, with no evidence of an 18p deletion. A novel inter-intrachromatid mechanism of formation of duplications and ring chromosomes is proposed. Although the effect of "ring instability syndrome" cannot be excluded, the phenotypes of our patients with characteristic features of 18q- and 18p- syndromes are compared and correlated with the analyzed genotypes. It has been observed that a short neck with absence of cardiac anomalies may be related to the deletion of the 18p material from the r(18) chromosome.

Ring chromosome 20 epilepsy syndrome in children Electroclinical features

Abstract: Article abstract— Ring chromosome 20 mosaicism is associated with dysmorphic features, mental retardation, and intractable seizures, including recurrent episodes of nonconvulsive status epilepticus. The authors’ findings in four children, all without dysmorphic features, indicate that mental deterioration and frequent subtle nocturnal frontal lobe seizures, associated with a characteristic EEG pattern, represent prominent additional clinical features not previously described in this syndrome. This emphasizes the importance of full-night video-EEG in children with frontal lobe seizures and cognitive deterioration.

Characterization of chromosomal abnormalities in uroepithelial carcinomas by G-banding, spectral karyotyping and FISH analysis.

Abstract: Chromosome analysis by G-banding, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) was per formed on 24 short-term cultured transitional cell bladder carcinomas and 5 cell lines established from bladder carcinomas. Except for one tumor with an apparently normal chromosomal constitution, clonal chromosome abnormalities were detected in all examined cases by the combined approach. The application of SKY and FISH techniques improved the karyotypic descriptions, originally based on C-banding only, by identifying 32 additional numerical changes, by establishing the chromosomal origin of 27 markers and 2 ring chromosomes, by redefining 53 aberrations and by detecting 15 hidden chromosomal rearrangements. No recurrent translocation, however, was detected. The most prominent: karyotypic feature was thus the occurrence of deletions and losses of whole chromosome copies indicating the importance of tumor suppressor genes in transitional cell carcinoma pathogenesis. Invasive carcinomas were karyotypically more complex than were low grade superficial tumors. Specific leases of material from chromosome 9 and from chromosome arms I Ip and 8p, and gains of 8q and Iq seem to be early changes appearing in superficial tumors, whereas losses from 4p and 17p and the formation of an isochromosome for 5p were associated with more aggressive tumor phenotypes. (Less)

Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: a fluorescence in situ hybridization and comparative genomic hybridization analysis.

Abstract: Cytogenetic analysis of Bednar tumor (pigmented dermatofibrosarcoma protuberans) has not been reported previously. Here, we report the identification of a supernumerary ring chromosome in a Bednar tumor by chromosome painting with fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Chromosome painting with FISH demonstrated that the supernumerary ring chromosome was composed of discontinuous, interwoven sequences from chromosomes 17 and 22. Amplification of chromosomes 17 and 22 sequences was confirmed by CGH. These results indicate that Bednar tumor and dermatofibrosarcoma protuberans are characterized by the same chromosomal features. To our knowledge, this is the first report that the ring chromosome in Bednar tumor is composed of amplified material from chromosomes 17 and 22.

How do tumors make ends meet

Abstract: When Barbara McClintock irradiated strains of Indian corn in the early 30s, she identified ring chromosomes, which she soon realized were a special case of chromosomes broken by radiation; the broken ends sometimes fused to one another and formed a ring (1, 2). This discovery led McClintock to hypothesize the existence of a special structure at the chromosome tip that would maintain chromosome stability. In 1941 she described the breakage-fusion-bridge cycle, a model for a repeating pattern of chromosome behavior that is triggered by an initial breakage (3). Normally, each chromatid strand has one centromere, and the chromosome ends remain capped by the telomeres that protect the ends from sticking to one another. But sometimes, harmful substances or radiation damage a chromatid and cause it to break. Without telomere caps, the new ends stick to each other, and the resulting fused chromosome has two centromeres as well as a duplication of some of the genes from that chromosome. When cell division occurs, the two centromeres of this unusual chromosome may be pulled to the opposite spindle poles of the cell, forming an irregular, long chromosome bridge between the two newly forming daughter cells (Fig. 1 A and B). Eventually, the abnormal chromatid breaks in two or may be left behind during cell division. If the chromosome ends are broken, they are likely to rejoin again, reforming a chromosome bridge at the next division.

Supernumerary marker chromosome (1) of paternal origin and maternal uniparental disomy 1 in a developmentally delayed child

Abstract: Editor—At least 168 cases with a supernumerary marker chromosome (SMC) from all chromosomes not including chromosome 15 have been documented.1 Birth prevalence is estimated at 0.14 to 0.72 per 1000.2 Subjects with a SMC have a partial trisomy (duplication) and in some cases a partial tetrasomy (triplication) of the genetic material contained in the SMC. The risk of an abnormal phenotype associated with a randomly ascertained de novo SMC derived from acrocentric autosomes (excluding chromosome 15) is estimated to be approximately 7% compared with approximately 28% for SMCs derived from non-acrocentric autosomes.1 The great variability of clinical findings in patients with SMCs originating from the same chromosome is probably the result of variation in size and genetic content, the degree of mosaicism, and uniparental disomy of the normal homologues of the chromosome from which the SMC derived. Evidence that subjects with SMCs might have an increased risk for UPD of the structurally normal homologues of the SMCs has been reported by several authors. To the best of our knowledge the coexistence of SMCs with UPD has been described for chromosomes 6, 7, 15, 20, and X.3-7 Here, we describe a further patient with multiple congenital anomalies, developmental delay, and the unique finding of coexistence of SMC 1 mosaicism and maternal uniparental disomy 1. The female patient was born at term after an uneventful pregnancy. At her birth, her mother was 33 years old and her father was 47 years old. Birth weight was 2500 g and length 49 cm. At the age of 6 years, she was investigated because of mental retardation. Height (1.14 m) and weight (17 kg) were within the normal range, but head circumference (44 cm) was far below the 3rd centile. Additional findings were temporal narrowing, downward slanting palpebral fissures, …

Molecular cytogenetic characterization of an acquired minute supernumerary marker chromosome as the sole abnormality in a case clinically diagnosed as atypical Philadelphia-negative chronic myelogenous leukaemia.

Abstract: A case of chronic myelogenous leukaemia (CML) in a 48-year-old man is reported. To the best of our knowledge, this is the first report of a Philadelphia-negative CML with an acquired small supernumerary marker chromosome (SMC) 11 as the sole abnormality. The derivative chromosome 11 was studied in detail using molecular cytogenetic methods; fluorescence in situ hybridization (FISH) using centromere- and region-specific probes for chromosome 11, microdissection, micro-comparative genomic hybridization (micro-CGH) and the recently developed multicolour banding (MCB) technique. The acquired SMC was determined to be a ring chromosome that can be described as r(11)(:p11.2-->q13.1:q14:).

Second trimester prenatal diagnosis of epignathus teratoma in ring X chromosome mosaicism with inactive ring X chromosome

Abstract: We report the second trimester prenatal echographic diagnosis of an epignathus teratoma in a female fetus with ring X chromosome mosaicism. The ring X chromosome mosaicism was present in the amniotic cell culture and in the teratoma and the ring X was inactive (X-inactive specific transcript (XIST) locus expressed). Hypoplastic left heart with valvular aortic stenosis and non-immune hydrops were additional findings, and are well-documented in Turner syndrome. The occurrence of epignathus teratoma in Turner syndrome has not been documented sofar.

Kabuki syndrome-like features associated with a small ring chromosome X and XIST gene expression.

Abstract: Although clinical features in Kabuki syndrome (KS; Niikawa-Kuroki syndrome) have been well defined, the underlying genetic mechanism still remains unclear. We report a 9-year-old girl with typical KS-like facial appearance, skeletal and dermatoglyphic abnormalities, severe mental retardation, and growth deficiency. In 60 of 100 GTG-banded metaphases from peripheral blood lymphocytes, a ring chromosome smaller than a G group chromosome was found, which, according to reverse painting, consisted of Xq11.1q13. The proband's karyotype was described as mos45,X/46,X,+r(X). Several loci were analyzed with fluorescence in situ hybridization (FISH) and microsatellite markers revealing that one r(X) breakpoint mapped proximal to DXS422 (Xp11.21) and the second mapped distal to XIST gene, between loci DXS128E and DXS441 (Xq13.2). Uniparental disomy for X and r(X) was excluded and the paternal origin of r(X) was identified. XIST expression was demonstrated by nested reverse transcription polymerase chain reaction (RT-PCR) using primers spanning exons 5, 6i, and 6 in RNA prepared from lymphocytes. The observation of XIST expression is in contrast to two other cases in which the XIST gene was either not present on r(X) or not expressed. To our knowledge, this is the first case of Kabuki-like syndrome manifestations with r(X) and XIST expression.

Molecular characterisation of a supernumerary ring chromosome in a patient with VATER association.

Abstract: Editor—Supernumerary marker chromosomes are rare with an incidence of 0.3-1.5/1000 newborns. Most carriers have a normal phenotype but in 15% of non-satellited marker cases mental retardation and minor anomalies have been reported.1 The origin of several supernumerary ring marker chromosomes has been identified by fluorescence in situ hybridisation (FISH).2 The VATER association is characterised by non-random occurrence of Vertebral anomalies, Anal atresia, Tracheo-oesophageal fistula with Esophageal atresia, Radial limb dysplasia, and Renal defects.3 The acronym VACTERL is used in cases with additional Cardiac and Limb malformations.4 VACTERL with hydrocephalus is thought to be an autosomal recessive disorder distinct from the VATER association.5 Other defects that occur less frequently have been also described.6 A defect in blastogenesis was suggested as a possible aetiology of this malformation spectrum. Martinez-Frias et al 7proposed that combinations of anomalies of blastogenetic origin, such as VATER/VACTERL, should be considered and called “polytopic field defects” instead of the generic term “association”. The knowledge that maternal intake of some teratogens, such as oestroprogestins8 or methimazole,9 may be associated with VATER/VACTERL in the newborn, probably affecting blastogenesis, and familial occurrence of VASTER/VACTERL10 11 suggest heterogeneity in the pathogenesis of the association, although it appears that the underlying causative event takes place at a very early stage of embryonic development. Only one chromosome abnormality has been described in VATER association, a patient with an interstitial 6q deletion,12while an additional case of VATER with 9qh+ has been reported.13 We report here an additional patient with malformations characteristic of VATER association and mosaicism for a small supernumerary ring chromosome derived from the pericentromeric region of chromosome 12. The proband was the term product of an uneventful pregnancy, requiring elective caesarean section because of uterine inertia. Birth weight …

Boy with bilateral retinoblastoma due to an unusual ring chromosome 13 with activation of a latent centromere.

Abstract: We present a patient with bilateral retinoblastoma and developmental delay who has an abnormal male karyotype containing 47 chromosomes, including an acentric derivative chromosome 13. We postulate that the derivative 13 occurred after a break at 13q14, with the proximal portion of the chromosome forming a ring and the distal portion undergoing duplication. Thus, this patient is trisomic for 13q14-->qter. The derivative chromosome with duplicated distal portion (13q14-->qter) lacked the 13 centromere and was negative for chromosome 13 alpha-satellite DNA by low stringency FISH. Nevertheless, this chromosome is stably transmitted in lymphocytes and fibroblasts. A single primary constriction was observed at band 13q21, consistent with activation of a latent centromere (neocentromere) at this band. The neocentromere on der(13) was positive for multiple centromeric proteins, suggesting that it acts as the functional centromere. By FISH, the Rb gene was present on the normal 13, the proximally derived ring chromosome, but not on the derivative chromosome. Although there was no evidence for disruption of the Rb gene, this chromosome rearrangement most likely results in abnormal expression of the Rb gene product.

Ring 20 chromosome syndrome with epilepsy and dysmorphic features: a case report.

Abstract: Summary: Relatively few cases of the 20 ring chromosome [r(20)] syndrome have been reported. Epileptic seizures, behavioral problems, mental retardation, and absence of definite dysmorphic features characterize this syndrome. We present a patient with the classic genetic and phenotypic findings. A 42-month-old boy with mild dysmorphic features and psychomotor retardation has had generalized tonic–clonic seizures, resistant to antiepileptic drug therapy since he was 26 months old. Electroencephalography (EEG) was performed on several occasions, as were brainstem auditory evoked potentials (BAEPs), magnetic resonance imaging (MRI), and cytogenetic studies. The EEG showed slow waves in anterior regions intermingled with spikes in temporal areas. The BAEPs were abnormal, and neuroimaging studies were normal. The chromosome r(20) appeared in 100 metaphases studied. Parental chromosomes were of normal karyotype. The genetic and EEG finding from this patient strongly suggest that epilepsy associated with 20 ring chromosome syndrome is a distinct new entity, although the clinical manifestations may be broader than previously recognized.

Prenatal diagnosis of mosaic ring chromosome 13 with anencephaly.

Abstract: We report on the prenatal diagnosis, genetic analysis and clinical manifestations of a second-trimester fetus with mosaic ring chromosome 13 and anencephaly. A 35-year-old, gravida 3, para 2 woman was referred for genetic counselling at 23 weeks' gestation because of an elevated maternal serum alpha-fetoprotein level of 2.386 multiples of the median. Prenatal ultrasonography showed intrauterine growth retardation and anencephaly. Amniocentesis revealed a karyotype of de novo mos 46,xx,r(13)(p11q32)/45,xx,-r(13) [corrected] (77%/23%). Molecular genetic analysis by quantitative fluorescent polymerase chain reaction (PCR) with small tandem repeat markers specific for chromosome 13 rapidly confirmed the maternal origin of the aberrant chromosome and determined the breakpoint at 13q32 between D13S225 (present) and D13S147 (absent). Our present finding indicates that anencephaly can be due to mosaic r(13) with a terminal deletion of 13q32-13q34 and an additional secondary rearrangement of loss of r(13). We propose that cytogenetic analysis is beneficial and warranted in pregnancies with fetal neural tube defects.

Pure trisomy 10p resulting from an extra ring chromosome: Characterization by methods of advanced molecular cytogenetics

Abstract: With the use of advanced molecular cytogenetic techniques, we have identified an extra ring chromosome consisting of the entire short arm of chromosome 10 (10p) in a 9-month-old girl with multiple congenital anomalies. This case represents another cytogenetic mechanism leading to the formation of pure complete trisomy 10p, which has not been reported previously. Pure trisomy 10p is rare. This case will further delineate those features associated with trisomy 10p. © 2001 Wiley-Liss, Inc.

FISH characterization of a supernumerary r(1)(::cen-->q22::q22-->sq21::) chromosome associated with multiple anomalies and bilateral cataracts.

Abstract: We describe the case of a 15-year-old girl with multiple congenital anomalies, dysmorphic features, severe kyphoscoliosis, growth and mental retardation, and the absence of speech, in whom 35% of the cells carried a supernumerary ring chromosome 1. Fluorescence in situ hybridization (FISH) analysis using YAC/BAC clones spanning the region from 1p13 to 1q21 made it possible to determine the genomic content and structure of the ring(1), which was found to consist of the cytogenetic bands 1q21-22. A complex structure was delineated in the ring chromosome with a partial inverted duplication delimited by markers WI-7732 and WI-607, with WI-7396 and WI-8386 being the boundaries of the single copy segment. Comparison of the clinical signs of other patients with mosaic r(1) reported in the literature allowed the identification of a patient sharing a number of clinical signs including cataracts. Given that mutations of the GJA8 gene encoding connexin 50 (Cx50) and mapping to 1q21 have been associated with the presence of cataracts, it is possible that a gain in copy number or a rearrangement of GJA8 may contribute to cataracto-genesis.

Spectral karyotyping reveals 17;22 fusions in a cytogenetically atypical dermatofibrosarcoma protuberans with a large marker chromosome as a sole abnormality.

Abstract: The presence of an extra ring chromosome containing material from 17q and 22q, or, less frequently, a t(17;22)(q22;q13), is a cytogenetic hallmark of dermatofibrosarcoma protuberans (DFSP). However, occasionally tumors with other, atypical karyotypes are encountered. We describe a case of recurrent DFSP without a ring chromosome or a t(17;22) on standard cytogenetic analysis. In all cells analyzed by G-banding, an additional, large marker chromosome was present as a sole abnormality. This chromosome apparently included chromosome 8 or the 8q arm, but the origin of its remaining part could not be determined with certainty. To characterize further the abnormal chromosome, we applied spectral karyotyping (SKY). SKY confirmed the presence of an extra chromosome 8 or arm 8q in the marker and showed that its remaining part was composed of segments from chromosomes 7, 17, 21, and 22, with two copies of a 17;22 fusion. Our results and the literature data suggest that, in addition to a specific 17;22 fusion, amplification of material from chromosomes 17, 22, 8, 5, 7, and 21 may play a role in DFSP development and/or progression. Furthermore, our case demonstrates the usefulness of SKY in detection of a diagnostically relevant 17;22 fusion in DFSP patients who have unusual karyotypic features.

Chromosomal Genetic Disease: Structural Aberrations

Abstract: Structural chromosome rearrangements are changes in the physical structure of chromosomes that may result in birth defects, mental retardation and increased risk for infertility or pregnancy loss. Keywords: cytogenetics; inversions; insertions; deletions; duplications; isochromosomes; ring chromosomes; aneusomy; karyotype; contiguous gene syndromes; reciprocal translocations; robertsonian translocations; quadrivalent

Identification of a small supernumerary marker chromosome, r(2)(p10q11.2), and the problem of determining prognosis.

Abstract: The identification of small supernumerary marker chromosomes (SMCs) and the elucidation of their clinical significance remain two of the problems in classical human cytogenetics. We observed a small supernumerary ring in amniotic fluid cell cultures and identified its origin as r(2)(p10q11.2) and its extent by means of fluorescent in situ hybridisation (FISH). Uniparental disomy (UPD) was excluded by microsatellite analysis using polymorphic markers localised in the same region. On the basis of normal ultrasonographic checks, the patient decided to continue the pregnancy. A normal female was delivered at term and subsequent neonatal follow-ups confirmed the normal phenotype and development. In the present case, genetic counselling was not helpful because of the absence of reference cases. Detailed characterisation made it possible to correlate the normal baby phenotype with the trisomic 2p10-2q11.2 genomic region. Further molecular cytogenetic investigations of SMCs classified by DNA content and pregnancy outcome data should improve genetic counselling and risk evaluation.

Amplification of ribosomal RNA genes in acute myeloid leukemia

Abstract: Gene amplification is a relatively rare event in acute myeloid leukemia (AML). Double minutes (dmin) and homogeneously staining regions are well established phenomena as cytogenetic correlates of gene amplification. Recently, however, two additional mechanisms leading to gene amplification, i.e., segmental jumping translocations and formation of ring chromosomes, have been described. We report four patients with AML, in whom bone marrow cells exhibited amplifications of ribosomal RNA (rRNA) genes in the form of ring chromosomes or a hsr. In two patients, the MLL gene, and in one patient the CBFA2 gene were shown to be co-amplified with rRNA genes. In two of the four patients, multiple copies of alpha-satellite sequences of the centromeres 13 and 21, respectively, were also demonstrated. In three of the four patients, the clinical course was very aggressive, leading to death within 2–8 months. In these three patients, complex karyotype abnormalities were found, whereas the karyotype of Patient 4 was characterized only by supernumerary ring 21 chromosomes of different sizes and a trisomy 8 in half of the metaphases. Modes of origin and clinical significance of the amplification of rRNA genes are discussed. © 2001 Wiley-Liss, Inc.

Complete karyotype discrepancy between placental and fetal cells in a case of ring chromosome 18.

Abstract: A case of complete karyotype discrepancy between cultured chorionic villi and amniotic in addition to fetal cells is reported. Ring chromosome 18 and monosomy 18 mosaicism was detected after amniocentesis. The pregnancy was terminated in the 23rd gestational week. Cytogenetic analysis of cultured umbilical cord tissue after termination confirmed the finding of ring chromosome 18/monosomy 18 mosaicism. In cultured umbilical blood lymphocytes monosomic cells 45,-18 were not detected and the karyotype was 46,XY,r(18). In contrast, short-term and long-term cultured chorionic villi showed a normal male karyotype of 46,XY. Ultrasonographic examination revealed amniotic band syndrome and scoliosis in the caudal region of the spine.