Showing papers on "Ring chromosome published in 2005"

Molecular and phenotypic characterization of ring chromosome 22.

Abstract: We performed a phenotype study of 35 individuals (19 males, 16 females) with ring chromosome 22 or r(22) with a mean age of 10 years. In common with other studies, a phenotype of moderate-to-profound learning difficulties and delay or absence of speech affected all individuals with the exception of the case with the smallest deletion. Autistic traits were significantly associated with r(22), as shown by an autism screening questionnaire. Mild and variable dysmorphic features, predominantly craniofacial and distal limb, were observed. Internal organ involvement was uncommon. Even though ring chromosomes are reportedly associated with growth abnormalities, only 2 out of 24 individuals showed evidence of growth failure, while 2 showed accelerated growth. Chromosome 22 long arm deletions, as determined by hemizygosity for informative microsatellite markers, varied from <67 kb to 10.2 Mb in size (or <0.15 to 21% of total chromosome length), with no significant differences in the parental origin of the ring chromosome. Few phenotypic features correlated with deletion size suggesting a critical gene, or genes, of major effect lies close to the telomere. Loss of the SHANK3/PROSAP2 gene has been proposed to be responsible for the main neurological developmental deficits observed in 22q13 monosomies. This study supports this candidate gene by identifying a phenotypically normal r(22) individual whose ring chromosome does not disrupt SHANK3. All other r(22) individuals were hemizygous for SHANK3, and we propose it to be a candidate gene for autism or abnormal brain development.

Insights from genomic microarrays into structural chromosome rearrangements

Abstract: Array-based comparative genomic hybridization allows high-resolution screening of copy number abnormalities in the genome, and becomes an increasingly important tool to detect deletions and duplications in tumor and post-natal cytogenetics. Here we illustrate that genomic arrays can also provide novel clues regarding the structural basis of chromosome rearrangement, including instability and mechanisms of formation of ring chromosomes. We also showed that array results might impact the recurrence risks for relatives of affected individuals. Our data indicate that chromosome rearrangements frequently involve more breaks than current cytogenetic models assume.

Mitotic and meiotic behaviour of a naturally transmitted ring Y chromosome: reproductive risk evaluation.

Abstract: BACKGROUND: The mitotic and meiotic behaviour of a transmitted ring Y [r(Y)] chromosome from a father to his Klinefelter syndrome (KS) son, and the mechanism of ring formation are analysed herein. To our knowledge, this is the first reported case of natural transmission of an r(Y). METHODS and RESULTS: Amplification of X chromosome polymorphisms by PCR showed that the KS was of paternal origin. G-banding and fluorescence in situ hybridization (FISH) studies revealed a similar percentage of mosaicism in father and son by mitotic loss of r(Y). SRY gene and Y marker amplification by PCR, FISH with subtelomeric probes for Xp/Yp and Xq/Yq, and comparative genomic hybridization (CGH) analyses indicated the intactness of the Y chromosome from SRY to subtelomere Yq. FISH analysis of sperm from the father showed significantly higher frequencies (P < 0.005) for diploidy and for 6, 13, 18, 21, 22, XX, XY disomies than those observed in control donors. CONCLUSIONS: An r(Y) with low material loss can be naturally transmitted, showing similar mitotic behaviour in the offspring. The presence of an r(Y) chromosome in germinal cells increased the risk of fathering offspring with numerical abnormalities, even for chromosomes not involved in the arrangement.

Mosaicism and phenotype in ring chromosome 20 syndrome

Abstract: Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder characterized by epilepsy, mild to moderate mental impairment, and malformation. Patients generally show mosaicism in 1-100% of lymphocytes with r(20). We report here a patient with r(20) syndrome who exhibited mild phenotype with the small ratio of mosaicism (13%) with r(20). Although previous small-scale studies concluded that the mosaicism ratio was unrelated to clinical phenotype, our reassessment of all 57 reported cases has revealed that the ratio is significantly associated with age at seizure onset, intelligence quotient, and malformation, but not with the response of epilepsy to drug treatment. Our results provide important clinical information and prediction for r(20) syndrome.

FISH-mapping of telomeric 14q32 deletions: search for the cause of seizures.

Abstract: Ring chromosome 14 is a rare cytogenetic disorder. Individuals with r(14) generally have developmental delay and seizures. Other features include hypotonia, microcephaly, mild facial dysmorphism, and retinal pigmentation. Most of these features are also found in patients with linear terminal deletions of chromosome 14, except for seizures and retinal abnormalities. The objective of the study was to determine if deletion of a specific chromosome region is a possible explanation for the occurrence of seizures in patients with ring chromosome 14. Patients diagnosed either with r(14) (six patients) or a deletion of distal 14q (three patients) were analyzed by FISH (fluorescence in situ hybridization) with BAC probes. We observed differences in the size of deletions in the studied group. In two r(14) patients, we did not detect any deletion; the four other patients had deletions of various sizes, ranging from 0.8 Mb to 5 Mb. Two linear deletions were 3.2 Mb and 5.3 Mb in length, respectively; the third case had an interstitial deletion that did not overlap with the others. The deleted regions in ring chromosomes showed overlap with those in the two linear terminal deletions. We conclude that there is unlikely to be a specific deleted locus in 14q32.3 that predisposes r(14) patients to seizures or retinal pigmentation. The cause is probably related to the formation of the ring itself and the effect this may have on local chromatin structure. © 2005 Wiley-Liss, Inc.

Supernumerary ring chromosome 7 mosaicism: Case report, investigation of the gene content, and delineation of the phenotype

Abstract: We report a girl with severe retardation of expressive speech development carrying a small, supernumerary ring chromosome derived from the proximal region of the long arm of chromosome 7. The r(7) chromosome is present in 50% of lymphocytes. We also review the six additional cases with a supernumerary r(7) chromosome reported in the literature. Among these patients, a severe retardation of productive language capabilities is seen as a shared clinical feature, irrespective of the degree of mosaicism as detected in blood. The dysmorphisms in these patients are minor and no shared congenital abnormalities seen. We, therefore, recommend chromosomal investigations in children with unexplained, disproportionately retarded expressive speech performance. Because speech and language acquisition are subject to genetic influences, we investigated whether there are genes on the r(7) chromosome that may affect brain development or function in a dosage-dependent manner. We found that both in our patient and in four patients described by others, the supernumerary r(7) chromosome contains the region from the centromere up to marker D7S613 located at 7q11.23. We speculate that the effects on speech acquisition are mediated by the supernumerary copies of the STX1A and LIMK1 genes, which are both located in this region and known to suppress neurite growth when overexpressed in vitro.

Mosaic monosomy of a neocentric ring chromosome maps brachyphalangy and growth hormone deficiency to 13q31.1-13q32.3.

Abstract: We describe a boy with moderate intellectual disability associated with distinctive hand malformations (hypoplastic and angel-shaped middle phalanges) and partial growth hormone (GH) deficiency associated with mosaic deletion of 13q31.1-13q32.3. The deleted segment was mapped to a 20-Mb region bounded by BACs RP11-1143C2 and RP11-139C1, narrowing the previously described locus for hand malformations at this region and suggesting that a locus for GH deficiency is also present at this location. The deleted segment contains at least three candidate genes, glypican-5, FARP1 and SOX21, that may be contributing to the phenotype in this boy. In a significant proportion (approximately 50%) of cells, the deleted region is present as a supernumerary ring chromosome stabilized by the formation of a neocentromere at 13q31-q32, within a region with a known propensity for neocentromere formation. The ring chromosome appears to be prone to low-level misdivision and loss in vitro which, in vivo, must be countered by selection for the balanced karyotype because the level of mosaicism has remained stable over 13 years.

Narrowing the candidate region for congenital diaphragmatic hernia in chromosome 15q26: contradictory results.

Abstract: To the Editor: Subtelomeric screening and FISH analysis of a 13-year-old girl with severe mental retardation, intrauterine growth retardation, microcephaly, facial dysmorphisms, hypoplastic kidney, and short hands and feet but without congenital diaphragmatic hernia (CDH [MIM 142340]) allowed us to find a de novo deletion in 15q26.1–26.2. That region, as shown by Klaassens et al. (2005) in a study published in the May issue of the Journal, contains a candidate region for CDH, a condition that occurrs in ∼1 of 3,000 newborns and is associated with a 30%–60% mortality rate, with significant morbidity among survivors (Harrison et al. 1994; Nobuhara et al. 1996). The etiology of this condition is barely known and, in most cases, is considered idiopathic, whereas ∼15% of patients with CDH show chromosomal abnormalities. Recently, Biggio et al. (2004) reported on a child with a 15q26.1 deletion showing CDH, coarctation of the aorta, and dysmorphic features, suggesting this region as the possible candidate locus for CDH. Furthermore, the authors proposed myocyte-specific enhancer factor–2A (MEF2A [MIM 600660]) as a candidate gene for CDH, coding for a protein playing a critical role in the control of muscle differentiation and development. Klaassens et al. (2005) found 7% numerical and 5% structural chromosome abnormalities in 200 CDH patients. The most frequent chromosome abnormality was 15q deletion. Eventually, they determined the size of the deletions in seven patients with CDH. They incorporated data from two patients with terminal 15q deletions without CDH, and data from one patient with a small 15q interstitial deletion and CDH. A minimal deletion region, spanning ∼5 Mb at chromosome bands 15q26.1–15q26.2, has been suggested by these authors. Two of the known genes of this region, namely, NR2F2 (MIM 107773) and CDH2 (MIM 602119), were considered to be the best candidates for CDH. To better define the deletion in our patient, FISH experiments were carried out with a set of linearly ordered BACs selected by human NCBI Map Viewer (build 35.1) and provided by the Sanger Institute. This analysis showed that the BAC RP11-386M24, localized to chromosome band 15q26.1 (∼9.0 Mb from the end of the chromosome), was the closest to the telomere that hybridized on both chromosomes in all examined metaphases. The immediately more centromeric CTD—2313J17 BAC showed signals of different intensities on the 15q telomeres, suggesting that the breakpoint lay within this BAC, whereas the overlapping RP11-437B10 BAC and all the distally placed BACs showed no hybridization signal (data not shown). We thus compared our results with the most significant previously characterized 15q deletions, including ring chromosome 15, unbalanced translocations, and pure 15qter monosomies, either associated with the CDH phenotype or not. As shown in figure 1, no clear critical region can be drawn from these data, essentially because case 12 with CDH carried a ring (15) resulting in a smaller deletion than cases 1, 2, and 3, without CDH. At least two hypotheses can be made to explain these contradictory data. First, it is possible that haploinsufficiency of the CDH locus has a reduced penetrance and that data from patients without CDH could be useless in establishing the critical region. If this is true, the candidate region is restricted to ∼3.5 Mb (fig. 1) and includes the NR2F2 gene, but its telomeric limit is more distal than that defined by Klaassens et al. (2005), which was derived from a deletion of a patient without CDH (fig. 1, case 13). On the other hand, drawing genotype-phenotype relationships may be difficult in ring carriers because of the potential instability of ring chromosomes that can be associated with gain or loss of genetic material in other tissues (Tumer et al. 2004). If we omit ring cases from the analysis, then the critical region would be narrowed to a 0.7-Mb genomic portion (fig. 1). The NR2F2 gene, in this case, would be located outside this putative critical region. Figure 1 Graphical representation of 15q deletions in patients with and without CDH. The most significant BAC clones analyzed are shown on the left. Solid boxes represent deleted regions, hatched boxes indicate the uncertainty of the breakpoints, and open boxes ... The ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sialyltransferase 2 gene (ST8SIA2 [MIM 602546]) is the unique known gene in this region and encodes for a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to the neural cell adhesion molecules (NCAMs) (Ong et al. 1998). The ST8SIA2 gene is expressed in many tissues during development (Angata et al. 1997). Evidence suggests that polysialylated NCAMs promote cell migration and, thus, they are thought to play a critical role in development. More specifically, it has been shown that, during diaphragmatic morphogenesis, the expression of polysialylated NCAMs is tightly modulated along each stage of myogenesis (Allan and Greer 1998). Finally, although it is less likely, we cannot exclude the possibility that both the mentioned hypotheses are true. In this case, the critical region would be represented by the extent of the deletion in patient 8 (fig. 1). Additional findings are needed to refine the search for a CDH gene in 15q chromosome. However, it seems likely that NR2F2 and ST8SIA2 are the best candidates.

FISH of supernumerary marker chromosomes (SMCs) identifies six diagnostically relevant intervals on chromosome 22q and a novel type of bisatellited SMC(22).

Abstract: Supernumerary marker chromosomes (SMCs) are frequently found at pre- and postnatal cytogenetic diagnosis and require identification. A disproportionally large subset of SMCs is derived from the human chromosome 22 and confers tri- or tetrasomy for the cat eye chromosomal region (CECR, the proximal 2 Mb of chromosome 22q) and/or other segments of 22q. Using fluorescence in situ hybridization (FISH) and 15 different DNA probes, we studied nine unrelated patients with an SMC(22) that contained the CECR. Five patients showed the small (type I) cat eye syndrome (CES) chromosome and each one had the larger (type II) CES chromosome, small ring chromosome 22, der(22)t(11;22) extrachromosome, and a novel type of bisatellited SMC(22) with breakpoints outside the low-copy repeats (LCRs22). By size and morphology, the novel bisatellited SMC(22) resembled the typical (types I and II) CES chromosomes, but it might have been associated with the chromosome 22q duplication syndrome, not CES. This SMC included a marker from band 22q12.3 and conferred only one extra copy each of the 22 centromere, CECR, and common 22q11 deletion area. There has been no previous report of a bisatellited SMC(22) predicting the chromosome 22q duplication syndrome. Accounting for the cytogenetic resemblance to CES chromosomes but different makeup and prognosis, we propose naming this an atypical (type III) CES chromosome. In this study, we found six distinct intervals on 22q to be relevant for FISH diagnostics. We propose to characterize SMCs(22) using DNA probes corresponding to these intervals.

Structural Chromosome Rearrangements

Abstract: The subject of structural chromosome rearrangements is an immense one, to which entire catalogs have been devoted. Indeed, there are theoretically an almost infinite number of ways in which chromosomes can reconfigure themselves from the normal 23-pair arrangement with which we are familiar. Although we tend to think of the resulting structural rearrangements in terms of chromosome pathology, some rearrangements are fairly innocuous. In fact, a few such benign rearrangements (such as certain pericentric inversions of chromosome 9) are seen frequently enough to be considered polymorphic variants of no clinical significance.

Ring chromosome 9 [r(9)(p24q34)]: a report of two cases.

Abstract: We report clinical and molecular cytogenetic studies in two patients with ring chromosome 9. Cytogenetics and fluorescent in situ hybridization (FISH) analysis using the p16 gene probe on 9p21, the ABL gene on 9q34, chromosome 9 alpha satellite-centromeric probes, and TelVision 9p and 9q probes which identify subtelomere-specific sequences on chromosome 9p and 9q, revealed 46,XX,r(9)(p24q34).ish r(9)(305J7-T7-,p16+,ABL+, D9S325-) and 46XY,r(9)(p24q34).ish r(9)(305J7-T7-,p16+,ABL+, D9S325-). Based on FISH analysis at least 115 kb was deleted on terminal 9p, and at least 95 kb from terminal 9q. In comparison with other reports of r(9), deletion 9p, and deletion 9q, both patients had clinical characteristics of ring 9 and additional features of deletion 9q or deletion 9p syndrome. The variability between the two cases with r(9) despite similar breakpoints identified by GTG-banding and FISH may be explained by submicroscopic differences between deletion breakpoints, ring instability, interaction of other genes on the phenotype, and variation in fetal environmental conditions.

[Turner's syndrome--correlation between karyotype and phenotype].

Abstract: Turner's syndrome is defined as a congenital disease determining by quantitative and/or structural aberrations of one from two X chromosomes with frequent presence of mosaicism. Clinically it is characterized by growth and body proportion abnormalities, gonadal dysgenesis resulting in sexual infantilism, primary amenorrhoea, infertility, characteristic stigmata, anomalies of heart, renal and bones and the presence of some diseases like Hashimoto thyroiditis with hypothyroidism, diabetes mellitus type 2, osteoporosis, hypertension. Turner's syndrome occurs in 1:2000 to 1:2500 female livebirth. The most frequent X chromosome aberrations in patients with phenotype of Turner syndrome are as follows: X monosomy - 45,X; mosaicism (50-75%), including 45,X/46,XX (10-15%), 45,X/46,XY (2-6%), 45,X/46,X,i(Xq), 45,X/46,X,del(Xp), 45,X/46,XX/47,XXX; aberration of X structure: total or partial deletion of short arm of X chromosome (46,X,del(Xp)) isochromosom of long arm of X chromosome (46,X,(i(Xq)), ring chromosome (46, X,r(X)), marker chromosome (46,X+m). Searching of X chromosome and mapping and sequencing of genes located at this chromosome (such as SHOX, ODG2, VSPA, SOX 3) have made possible to look for linkage between phenotypes and adequate genes or regions of X chromosome. In this paper current data concerning correlation between phenotype and karyotype in patients with TS have been presented.

Interstitial deletion 11(p11.12p11.2) and analphoid marker formation results in inherited Potocki-Shaffer syndrome.

Abstract: We report a family with inherited Potocki-Shaffer syndrome. The phenotypically normal mother has an interstitial deletion of 11(p11.12p11.2) with neocentric marker chromosome formation. The marker chromosome contains the deleted material on 11p11.2 and is likely a ring. The patient inherited a maternal deleted chromosome 11 but not the marker chromosome, thus resulting in an unbalanced karyotype along with the phenotype of Potocki-Shaffer syndrome. The deleted region in our case-11p11.12p11.2-is a newly reported site of constitutional neocentromere formation. This is also the first report describing deletion of 11p11.12-p11.2 and neocentromere formation resulting in inherited Potocki-Shaffer syndrome.

« Ring syndrome» involving chromosome 2 confirmed by fish analysis using chromosome-specific subtelomeric probes

Abstract: "Ring syndrome" is described as those cases with complete ring chromosomes showing, independently of the chromosome involved, severe growth failure, minor dysmorphic features, and mild-to-moderate mental retardation, without major malformations. We present a girl with ring 2 chromosome, exhibiting severe growth failure, minor dysmorphic features, spontaneously closed ventricular septum defect, and normal development. G-banding chromosome analysis and fluorescence in situ hybridization (FISH) analysis using chromosome-specific subtelomeric probes (2ptel, 2qtel) demonstrated the major karyotype as 46,XX,r(2)(p25.3q37.3).ish r(2)(2ptel+,2qtel+). We review the cases with "ring syndrome" confirmed by FISH using chromosome-specific subtelomeric probes, suggesting that this method might be useful to predict developmental prognosis in a case with an apparently complete ring chromosome.

Molecular cytogenetic characterization of a de novo supernumerary ring chromosome 7 resulting in partial trisomy, tetrasomy, and hexasomy in a child with dysmorphic signs, congenital heart defect, and developmental delay.

Abstract: We report on a girl with mosaicism (65%) of a de novo supernumerary ring chromosome 7. The main clinical features were delayed psychomotor development, congenital heart defect, facial dysmorphisms, and long hands, fingers, feet and toes. Molecular cytogenetic analysis revealed that the ring chromosome was duplicated in 20% of the analyzed metaphases with marker chromosome and quadruplicated in 5% thereof. Uniparental disomy (UPD) of the two normal sister chromosomes 7 was excluded. This is, to our knowledge, the first report of a partial tetrasomy to hexasomy due to a ring chromosome 7. Additionally, the ring evolution could be reconstructed according to the FISH-results.

Association of microcephaly and cafe-au-lait spots in a patient with ring chromosome 12 syndrome.

Abstract: We describe a patient who was evaluated because of delayed development. The patient had microcephaly and cafe-au-lait spots and the facial features included upward slanting of the palpebral fissures, short nasal bridge and a highly arched palate. In addition the external ears had bilateral over folded helices, there was clinodactyly of the fourth and fifth fingers and multiple cafe-au-lait spots on the back, buttocks and thighs. Chromosomal analysis of peripheral blood showed 46,XY,-r(12)(p13.3q24.33)[73]/45,XY,-12[8]/47,XY,r(12)(p13.3q24.33),+r(12)(p13.3q24.33)[2]. This is the eighth case of a patient with a ring chromosome 12 to be reported so far. The similarity of our patient to those previously described suggests that the ring chromosome 12 syndrome can be delineated as a distinct entity with characteristic clinical features.

Duplication of the Down syndrome critical region does not predict facial phenotype in a baby with a ring chromosome 21.

Abstract: Ring chromosomes represent a rare type of chromosomal anomaly that can lead to multiple malformations. Although rings may occur with any chromosome, ring chromosome 21 is of particular interest due to the association of this chromosome with Down syndrome. Individuals with a ring chromosome 21, containing duplicated material, typically have a phenotype consistent with Down syndrome. We report an infant with a ring chromosome 21 containing a duplication of most of the long arm, including the Down syndrome critical region [46,XX,r(21)(p11.2q22.3)]. Fluorescence in situ hybridization analyses of the ring showed one chromosome 21 centromere, two copies each of the AML1 gene (q22) and the Down syndrome critical region, and deleted subtelomeric material. The patient has some Down syndrome characteristics including a high arched palate, a secundum atrial septal defect, and duodenal stenosis, but lacks the typical Down syndrome facial features, nuchal folds, and hand/foot anomalies. The phenotype of this patient supports the hypothesis that the duplication of the Down syndrome critical region alone is not sufficient to recapitulate the classical Down syndrome craniofacial phenotype.

A patient with a ring chromosome 2 and microdeletion of 2q detected using FISH: Further support for “ring chromosome 2 syndrome”

Abstract: Ring chromosomes, formed when a chromosome undergoes two breaks and the broken ends of the chromosome reunite in a ring structure, are quite rare but have been detected for every human chromosome [Nussbaum, 2001]. Ring chromosome 2 has been reported in 10 cases [Sutherland and Carter, 1978; Maraschio et al., 1979; Vigfusson et al., 1980; Cote et al., 1981; Jansen et al., 1982; Wyandt et al., 1982; Lacassie et al., 1999; Dee et al., 2001]. We describe a newborn male with facial dysmorphism and multiple congenital anomalies who has a ring chromosome 2, in addition to a terminal 2q deletion. The greater resemblance our patient has to patients with ring chromosome 2, than to those with isolated terminal 2q deletion, further supports the existence of a unique ring chromosome 2 syndrome. Our patient was born to a healthy 30-year-old woman whose pregnancy was complicated by severe oligohydramnios detected at 41 weeks of gestation, which prompted a cesarean section delivery. Following delivery, he developed persistent tachypnea necessitating admission to the special care nursery. Chest radiograph was normal. Echocardiogram showed multiple large muscular VSDs, hypoplastic transverse aortic arch and isthmus, and moderate patent ductus arteriosus with right to left flow in systole. Physical examination was significant for length and weight below 3rd centiles, and head circumference significantly below 3rd centile at 29.5 cm. Dysmorphic findings (Fig. 1) included blepharophimosis, upslanting palpebral fissures, epicanthal folds, prominent arched eyebrows, anteverted nares, long philtrum, micrognathia, short neck, high posterior hair line, bilateral clinodactyly of the 5th fingers, and unusually long great toes. Successful surgical repair of his cardiac anomalies at 5 days of age was followed by uneventful postoperative recovery and he was discharged home at 2 weeks of age on a nasogastric tube feeding regimen. Cytogenetic analysis of cultured peripheral blood lymphocytes showed a male karyotype mosaicism for a ring chromosome 2 in 26 metaphases out of 30 analyzed. Cytogenetic analysis of 20 metaphases from fibroblast cultures prepared from a skin biopsy showed a mosaic pattern for four different cell lines: (1) ring chromosome 2 in 13 metaphases, (2) monosomy chromosome 2 in 4 metaphases, (3) two ring chromosomes 2 in each of 2 metaphases, and (4) double ring chromosome 2 in 1 metaphase. Fluorescence in situ hybridization (FISH) was performed using Vysis TelVysion subtelomere probes for both arms and whole chromosome paint for chromosome 2. The subtelomeric probe specific to the short arm of chromosome 2 (2p Subtel) displayed no deletion of this region in the ring 2. The subtelomeric probe specific to the long arm of chromosome 2 (D2S447) showed a deletion of this region in the ring 2 (Fig. 2). Whole chromosome paint 2 (B10) was used to confirm that there was no evidence of any other chromosomal material other than chromosome 2 in the ring chromosome 2 (data not shown). The final fibroblast karyotype is 46,XY,r(2)(p25q37)[13]/45,XY, 2[4]/47,XY,r(2)(p25q37)x2[2]/ 46,XY,dic r(2;2)(p25q37;p25q37)[1].ish r(2)(wcp2þ,2p subtelþ, 2q subtel ). FISH performed on the peripheral blood lymphocytes also detected the deletion of the 2q terminus in the ring structure (data not shown). Table I shows the striking similarity between our patient and the previously reviewed cases of ring chromosome 2 by Dee et al. [2001]. The finding of a 2q37 terminal deletion is unusual. Indeed, Dee et al. [2001], who noted that none of the previously reported cases of ring 2 were studied using FISH, could not detect any deletion involving 2q. Wyandt et al. reported a patient with mild mental retardation and facial dysmorphism whose peripheral blood lymphocytes were mosaic for duplication of 2q33.3!2qter [70%] and ring chromosome 2p [2p25.2! 2q33.2] [30%]. The ring chromosome appeared to have a terminal deletion from 2q33.3!2qter. Wyandt’s case, however, was different from other ring 2 cases because the duplication was believed to be the dominant etiological factor for the phenotype and not the ring structure [Wyandt et al., 1982]. Chromosome 2q37 terminal deletion, without ring formation, has been reported in a number of cases, the phenotype of which has been reviewed by a number of authors [Conrad et al., 1995; Batstone et al., 2003; Daniel et al., 2003; Aldred et al., 2004]. Interestingly, our patient had little resemblance in his phenotype to that reported in terminal deletion of 2q37 without ring structure. Conrad et al., for example, listed macrocephaly and frontal bossing as the main features in his review, features not present in our patient. Similarly, microcephaly, a prominent feature in our patient, was not seen in any of the patients reviewed by Daniel et al. or Batstone et al. and was seen in only 1 out of 20 patients reviewed by Aldred et al. Interestingly, there are recent reports of the development of Albright hereditary osteodystrophy [AHO]-like syndrome in a relatively high frequency in patients with 2q37 deletion [Giardino et al., 2003; Aldred et al., 2004; Chassaing et al., 2004]. Our patient did not have features such as brachydactyly or subcutaneous calcification that would suggest AHO-like syndrome. However, the phenotype of AHO-like may not be evident before adolescence [Chassaing et al., 2004], and long term follow up of our patient is needed before one can rule this out. It seems, therefore, that ring 2 confers more influence on our patient’s phenotype than the 2q37 deletion. Indeed, Dee et al. [2001] made a similar observation when they noted that the phenotype of their patient with a ring 2 with concurrent 2p deletion was more similar to other reports of ring 2 than to those with 2p deletion only. This lends further support to the suggestion of Cote et al. [1981] that the resulting phenotypic effect of ring *Correspondence to: Fowzan S. Alkuraya, M.D., Division of Genetics and Metabolism, Children’s Hospital Boston, Harvard Medical School, Fegan 10, 300 Longwood Avenue, Boston, MA 02115. E-mail: Fowzan.Alkuraya@childrens.harvard.edu.

Pure trisomy 19p syndrome in an infant with an extra ring chromosome.

Abstract: We report a 12-month-old infant evaluated for severe hypotonia, psychomotor retardation, and facial dysmorphisms, including round face, high prominent forehead, downward slanted palpebral fissures, hypertelorism, short nose, chubby cheeks, long philtrum, anteverted lower lip, low-set asymmetric and dysmorphic ears. Karyotype analysis disclosed an extra mosaic ring chromosome, which included the whole 19p arm. Four additional patients with supernumerary ring 19 chromosomes have been reported, but none of them had pure trisomy 19p.

Short communication Chromosome 7 abnormalities in acute megakaryoblastic leukemia associated with Down syndrome

Abstract: A 2-year-old girl with Down syndrome (DS) developed acute megakaryoblastic leukemia (AMKL) following a transient myeloproliferative disorder (TMD). The blast cells showed an altered karyotype of 47,XX,r(7),21c. Serial cytogenetic studies during the course of the illness showed rapid stepwise clonal chromosome changes, including a ring chromosome 7, associated with treatment refractoriness. We reviewed 10 published cases of Down syndrome-related AMKL (DS-AMKL) showing chromosome 7 abnormalities and found that these changes do not carry the same prognostic weight as for non-DS children. For DS-AMKL, therefore, other prognostic factors besides clonal cytogenetic changes need to be identified for planning optimal therapy. 2005 Elsevier Inc. All rights reserved.

Ring chromosome 4 in a patient with early onset type 2 diabetes, deafness, and developmental delay

Abstract: To date, most ring formations of chromosome 4 lose distal 4p and usually include the Wolf-Hirschhorn syndrome region [WHS]. We describe a case with r(4) in a girl who presented without features of WHS; she had mild developmental delay, deafness, short stature, obesity, and the onset of type 2 diabetes in adolescence, a distinctive phenotype. Although 4p was significantly deleted on Giemsa banding, the 4p junction was distal to the WHS and FGFR3 but proximal to the D4S3360 marker. The 4q breakpoint was close to the telomere. The phenotype appears different from previous patients with 4p- or r(4), which have had more extensive 4p deletion.

Supernumerary ring chromosome 20 in a mother and her child.

Abstract: The authors report a familial case of mosaicism for an extra ring 20, identified by fluorescence in situ hybridization (FISH), in a mother and her child. In spite of the fact that both patients had clinical abnormalities, the more severe phenotype present in the child was probably due to the higher percentage of abnormal cells. To our knowledge, this is the first report of a familial extra ring 20 mosaicism. © 2005 Wiley-Liss, Inc.

Molecular cytogenetic characterization of ring chromosome 4 in a female having a chromosomally normal child.

Abstract: We present the clinical and molecular findings of mosaic ring chromosome 4. The patient was referred to us for infertility and short stature. Results of three repeated cytogenetic analyses from lympho

First small supernumerary ring chromosome carrying 10q euchromatin in a patient with mild phenotype characterized by molecular cytogenetic techniques and review of the literature.

Abstract: We report the identification and characterization of the first supernumerary ring chromosome 10 containing a considerable proportion of 10q euchromatin by microdissection and reverse painting in a female patient presenting with short stature. Fluorescence in situ hybridization studies showed that the marker chromosome originates from chromosome 10 and includes the euchromatic bands p11.2 and q11.2. The supernumerary marker chromosome 10 was found in 14% of the peripheral blood lymphocytes analyzed. This constitutional mosaic could be confirmed in oral mucosa cells as a second cell system (16%) by interphase FISH using an alphoid centromeric probe for chromosome 10. Parental karyotypes were normal, uniparental disomy for the normal chromosomes 10 could be excluded by microsatellite analysis. The karyotype of the patient detected in peripheral blood cells can be described as mos 47,XX,+mar.rev ish r(10)(p11.2q11.2)(wcp10+,cep10+)/46,XX.

Supernumerary der(1) marker chromosome derived from a ring chromosome 1 which has retained the original centromere and euchromatin from 1q21.1 → q21.3 with substantial loss of 1q12 heterochromatin in a female with dysmorphic features and psychomotoric developmental delay

Abstract: We report on a 5.5-year-old girl with dysmorphic features and psychomotoric developmental delay with a mitotically stable supernumerary marker chromosome. The origin of the marker was identified by microdissection and reverse painting of marker DNA as the pericentromeric region of chromosome 1. Fine mapping by FISH with selected YAC or BAC clones identified no p-arm material on the marker. The marker has retained its original centromere and euchromatin from 1q21.1-q21.3 but only small remnants of the 1q12 heterochromatin. Furthermore, some FISH clones presented single signals on the marker and others presented double signals indicating a partial duplication within the marker. These observations suggest a multi-step origin of the marker most probably with ring formation as the first step.