Showing papers on "Ring chromosome published in 2015"
TL;DR: The genomic features of chromothripsis are reviewed and recent progress on understanding its mechanism is summarized, including new work indicating that one mechanism to generate chromothRIpsis is through the physical isolation of chromosomes in abnormal nuclear structures (micronuclei).
Abstract: Chromosomal rearrangements are generally thought to accumulate gradually over many generations. However, DNA sequencing of cancer and congenital disorders uncovered a new pattern in which multiple rearrangements arise all at once. The most striking example, chromothripsis, is characterized by tens or hundreds of rearrangements confined to a single chromosome or to local regions over a few chromosomes. Genomic analysis of chromothripsis and the search for its biological mechanism have led to new insights on how chromosome segregation errors can generate mutagenesis and changes to the karyotype. Here, we review the genomic features of chromothripsis and summarize recent progress on understanding its mechanism. This includes reviewing new work indicating that one mechanism to generate chromothripsis is through the physical isolation of chromosomes in abnormal nuclear structures (micronuclei). We also discuss connections revealed by recent genomic analysis of cancers between chromothripsis, chromosome bridges, and ring chromosomes.
156 citations
TL;DR: Familial transmission of rings from carrier to offspring has been described and prenatal diagnosis for any pregnancies should always be considered, of interest is ring chromosome 20 which has a significant association with epilepsy with seizure onset in early childhood.
Abstract: Ring chromosomes arise following breakage and rejoining in both chromosome arms. They are heterogeneous with variable size and genetic content and can originate from any chromosome. Phenotypes associated with ring chromosomes are highly variable as apart from any deletion caused by ring formation, imbalances from ring instability can also occur. Of interest is ring chromosome 20 which has a significant association with epilepsy with seizure onset in early childhood. Severe growth deficiency without major malformations is a common finding in the ring chromosome carrier. This phenotype associated with ring behaviour and mitotic instability and independent of the chromosome involved has been termed the “ring syndrome”. Precise genotype-phenotype correlations for ring chromosomes may not be possible as influencing factors vary depending on the extent of deletion in ring formation, ring instability and the level of mosaicism. Although ring chromosomes usually arise as de novo events, familial transmission of rings from carrier to offspring has been described and prenatal diagnosis for any pregnancies should always be considered.
42 citations
TL;DR: It is demonstrated that the iPSC technique holds the potential to correct X monosomy, but the correction rate is very low, probably due to differential regulation of cell cycle genes between individuals.
Abstract: The human induced pluripotent stem cell (iPSC) technique promises to provide an unlimited, reliable source of genetically matched pluripotent cells for personalized therapy and disease modeling. Recently, it is observed that cells with ring chromosomes 13 or 17 autonomously correct the defects via compensatory uniparental disomy during cellular reprogramming to iPSCs. This breakthrough finding suggests a potential therapeutic approach to repair large-scale chromosomal aberrations. However, due to the scarceness of ring chromosome samples, the reproducibility of this approach in different individuals is not carefully evaluated yet. Moreover, the underlying mechanism and the applicability to other types of chromosomal aberrations remain unknown. Here we generated iPSCs from four 45,X chorionic villous fibroblast lines and found that only one reprogrammed line acquired 46,XX karyotype via uniparental disomy of the entire X chromosome. The karyotype correction was reproducible in the same cell line by either retroviral or episomal reprogramming. The karyotype-corrected iPSCs were subject to X chromosome inactivation and obtained better colony morphology and higher proliferation rate than other uncorrected ones. Further transcriptomic comparison among the fibroblast lines identified a distinct expression pattern of cell cycle regulators in the uncorrectable ones. These findings demonstrate that the iPSC technique holds the potential to correct X monosomy, but the correction rate is very low, probably due to differential regulation of cell cycle genes between individuals. Our data strongly suggest that more systematic investigations are needed before defining the iPSC technique as a novel means of chromosome therapy.
21 citations
TL;DR: Two unrelated patients with terminal deletions in the long arm of chromosome 13 showing brain malformation consisting of holoprosencephaly and cerebellar vermis hypoplasia are described, providing further evidence that 13Q32.2q32.3 deletion, harboring ZIC2 and ZIC5, leads to Cerebellar dysgenesis.
Abstract: We describe two unrelated patients with terminal deletions in the long arm of chromosome 13 showing brain malformation consisting of holoprosencephaly and cerebellar vermis hypoplasia. Array comparative genomic hybridization analysis revealed a pure terminal deletion of 13q31.3q34 in one patient and a mosaic ring chromosome with 13q32.2q34 deletion in the other. Mutations in ZIC2, located within region 13q32, cause holoprosencephaly, whereas the 13q32.2q32.3 region is associated with cerebellar vermis hypoplasia (Dandy-Walker syndrome). The rare concurrence of these major brain malformations in our patients provides further evidence that 13q32.2q32.3 deletion, harboring ZIC2 and ZIC5, leads to cerebellar dysgenesis.
16 citations
TL;DR: It is found that dynamic ring mosaicism is unlikely to be a major cause of phenotypic variability in the ring 18 population, and the importance of molecular and cytogenetic analysis to determine both chromosome content and morphology is confirmed.
Abstract: Ring chromosome 18 is a rare condition which has predominantly been described by case reports and small case series. We assessed a cohort of 30 individuals with ring 18 using both microarray comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH). We determined that each participant had a unique combination of hemizygosity for the p and q arms. Four ring chromosomes had no detectable deletion of one of the chromosome arms using aCGH. However, two of these ring chromosomes had telomeric sequences detected using FISH. These data confirm the importance of molecular and cytogenetic analysis to determine both chromosome content and morphology. We failed to find dramatic changes in mosaicism percentage between cytogenetic measurements made at the time of diagnosis and those made years later at the time of this study, demonstrating that dynamic ring mosaicism is unlikely to be a major cause of phenotypic variability in the ring 18 population. Lastly, we present data on the clinical features present in our cohort, though the extreme genotypic variability makes it impossible to draw direct genotype-phenotype correlations. Future work will focus on determining the role of specific hemizygous genes in order to create individualized projections of the effect of each person's specific ring 18 compliment.
14 citations
TL;DR: Nine breakpoint cluster regions potentially involved in the genesis of RGM chromosomes turned out to be significantly enriched in poly‐pyrimidine traits, which indicated a potential functional constraint in the amplification process of sarcomas.
Abstract: Gene amplification is relatively common in tumors. In certain subtypes of sarcoma, it often occurs in the form of ring and/or giant rod-shaped marker (RGM) chromosomes whose mitotic stability is frequently rescued by ectopic novel centromeres (neocentromeres). Little is known about the origin and structure of these RGM chromosomes, including how they arise, their internal organization, and which sequences underlie the neocentromeres. To address these questions, 42 sarcomas with RGM chromosomes were investigated to detect regions prone to double strand breaks and possible functional or structural constraints driving the amplification process. We found nine breakpoint cluster regions potentially involved in the genesis of RGM chromosomes, which turned out to be significantly enriched in poly-pyrimidine traits. Some of the clusters were located close to genes already known to be relevant for sarcomas, thus indicating a potential functional constraint, while others mapped to transcriptionally inactive chromatin domains enriched in heterochromatic sites. Of note, five neocentromeres were identified after analyzing 13 of the cases by fluorescent in situ hybridization. ChIP-on-chip analysis with antibodies against the centromeric protein CENP-A showed that they were a patchwork of small genomic segments derived from different chromosomes, likely joint to form a contiguous sequence during the amplification process. © 2014 Wiley Periodicals, Inc.
9 citations
TL;DR: The phenotypic overlap between the present case, the FOXG1 syndrome and the r(14) syndrome supports that dysregulation ofFOXG1 may contribute to the classical r( 14)-syndrome, likely mediated by dynamic mosaicism.
Abstract: In this study we performed molecular characterization of a patient with an extra ring chromosome derived from chromosome 14, with severe intellectual disability, epilepsy, cerebral paresis, tetraplegia, osteoporosis and severe thoraco-lumbal scoliosis. Array CGH analysis did not show any genomic imbalance but conventional karyotyping and FISH analysis revealed the presence of an interstitial 14q12q24.3 deletion and an extra ring chromosome derived from the deleted material. The deletion and ring chromosome breakpoints were identified at base-pair level by mate-pair and Sanger sequencing. Both breakpoints disrupted putative long non-coding RNA genes (TCONS00022561;RP11-148E17.1) of unknown function. However, the proximal breakpoint was 225 kb downstream of the forkhead box G1 gene (FOXG1), within the known regulatory landscape of FOXG1. The patient represents the first case of a r(14) arising from an interstitial excision where the phenotype is compatible with dysregulation of FOXG1. In turn, the phenotypic overlap between the present case, the FOXG1 syndrome and the r(14) syndrome supports that dysregulation of FOXG1 may contribute to the classical r(14)-syndrome, likely mediated by dynamic mosaicism.
7 citations
TL;DR: Combined karyotyping, aCGH and MS-MLPA analyses are effective to define the copy number changes and methylation patterns for sSMC(15)s in a clinical setting and could lead to further gene expression profiling for better phenotype correlation.
Abstract: The low copy repeats (LCRs) in chromosome 15q11-q13 have been recognized as breakpoints (BP) for not only intrachromosomal deletions and duplications but also small supernumerary marker chromosomes 15, sSMC(15)s, in the forms of isodicentric chromosome or small ring chromosome. Further characterization of copy number changes and methylation patterns in these sSMC(15)s could lead to better understanding of their phenotypic consequences. Routine G-band karyotyping, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay were performed on two Chinese patients with a sSMC(15). Patient 1 showed an isodicentric 15, idic(15)(q13), containing symmetrically two copies of a 7.7 Mb segment of the 15q11-q13 region by a BP3::BP3 fusion. Patient 2 showed a ring chromosome 15, r(15)(q13), with alternative one-copy and two-copy segments spanning a 12.3 Mb region. The defined methylation pattern indicated that the idic(15)(q13) and the r(15)(q13) were maternally derived. Results from these two cases and other reported cases from literature indicated that combined karyotyping, aCGH and MS-MLPA analyses are effective to define the copy number changes and methylation patterns for sSMC(15)s in a clinical setting. The characterized genomic structure and epigenetic pattern of sSMC(15)s could lead to further gene expression profiling for better phenotype correlation.
7 citations
TL;DR: The clinical features of a child with a ring chromosome 10, associated with prenatal and postnatal growth retardation, microcephaly, dysmorphic features, hypotonia, heart defect, severe pes equinovarus, and bronchial asthma are reported.
Abstract: Ring chromosome 10 is a rare cytogenetic finding. Only a few cases with molecular cytogenetic definition have been reported. We report here on a child with a ring chromosome 10, which is associated with prenatal and postnatal growth retardation, microcephaly, dysmorphic features, hypotonia, heart defect, severe pes equinovarus, and bronchial asthma. The chromosomal aberration was defined by chromosome microarray analysis, which revealed two deletions at 10pter (3.68 Mb) and 10qter (4.26 Mb). The clinical features are very similar to those reported in other clinical cases with ring chromosome 10, excluding bronchial asthma, which has not been previously reported in individuals with ring chromosome 10.
6 citations
TL;DR: This is the first report of periventricular heterotopia and white matter abnormalities manifested in a patient with ring chromosome 6, and array-comparative genomic hybridization identified terminal deletion of 6q27 (1.5 Mb) and no deletion on 6p.
Abstract: Ring chromosome 6 is a rare chromosome abnormality that arises typically de novo. The phenotypes can be highly variable, ranging from almost normal to severe malformations and neurological defects. We report a case of a 3-year-old girl with mosaic ring chromosome 6 who presented with being small for gestational age and intellectual disability, and whose brain MRI later revealed periventricular heterotopia and white matter abnormalities. Mosaicism was identified in peripheral blood cells examined by standard G-bands, mos 46,XX,r(6)(p25q27)[67]/45,XX,-6[25]/46,XX,dic r(6:6)(p25q27:p25q27)[6]/47,XX,r(6)(p25q27) × 2[2]. Using array-comparative genomic hybridization, we identified terminal deletion of 6q27 (1.5 Mb) and no deletion on 6p. To our knowledge, this is the first report of periventricular heterotopia and white matter abnormalities manifested in a patient with ring chromosome 6. These central nervous system malformations are further discussed in relation to molecular genetics.
6 citations
TL;DR: The present case describes an azoospermic male with r(9) and this case further highlight that autosomal ring chromosomes can be involved in male infertility.
Abstract: Ring chromosome abnormalities are rare abnormalities potentially involving any chromosome and the vast majority of previously reported cases were seen in patients with various congenital malformations and mental retardation. On the other hand, only few subjects carrying ring chromosomes and with normal phenotype have been described [1]. Until now only 30 cases of ring autosome 9 (r(9)) have been reported in the literature [2]. The prevalence of this pathology is 1 in 50,000 foetuses and in the majority of cases serious malformations were described [3].
The most typical ring formation occurs after terminal deletion and fusion of the p arm and the q arm and under this process genetic material can be lost [4]. The most common breakpoints are found between 9p24-p22 and 9q33-q34, but end-to-end fusion of palindromic telomere sequences have also been reported [5].
The Danish cytogenetic register, which contains data from all cytogenetic testing in Denmark from 1960 onwards (altogether 345,000 cases), has sparse information on two r(9) cases: a female, born in 1946, who died childless and a girl born 2008 for whom no more information is available.
The most frequent malformations reported in connection with r(9) are related to the deleted regions of both arms and include growth and psychomotor retardation, facial dysmorphism, microcephaly, cardiac malformations, limb and skeletal anomalies [5]. Microdeletions in the telomeric region of the long arm of chromosome 9 were found in patients with Kleefstra syndrome [6, 7], whereas microdeletions of the telomeric end of the short arm may lead to 46,XY gonadal dysgenesis [2].
The literature regarding genital malformations in males with the presence of r(9) is very sparse; however the following malformations have previously been reported: cryptorchidism, hypospadias and micropenis [7]. Until now it is not clear whether the presence of r(9) affects spermatogenesis, as most cases have been described in young boys. Moreover, the literature is sparse regarding phenotypic details and sperm status. However azoospermia has previously been reported in males with other ring chromosomes, affecting chromosomes 12, 15, 21 and 22 [4, 8, 9].
The distal part of 9p is quite polymorphic and larger deletions of this region are often sporadic, combined with head/facial malformations like trigonocephaly, long philtrum, hypertelorism and micrognatia [2]. However, different gonadal disorders like complete gonadal dysgenesis, ovotestis, cryptorchidism and/or hypoplastic testes have also been described and typically these disorders were caused by deletions of three DMRT genes (DMRT1, DMRT2 and DMRT3) on the 9p24 region, with DMRT1 being the prime candidate [10]. These genes are involved in downstream pathways of sex determination; however the exact molecular mechanism is unclear.
The present case describes an azoospermic male with r(9) and this case further highlight that autosomal ring chromosomes can be involved in male infertility.
TL;DR: This report describes a new patient with a ring chromosome 2 completely characterised by array-CGH providing additional information useful not only to study genotype-phenotype correlation but also to validate the role of already reported candidate genes and to suggest novel ones which could improve the understanding of the clinical features associated with ring chromosomes 2.
Abstract: Background
Ring chromosome 2 is a rare constitutional abnormality that generally occurs de novo. About 14 cases have been described to date, but the vast majority of papers report exclusively conventional cytogenetic investigations and only two have been characterized by array-CGH.
TL;DR: This is the first case of non-reciprocal translocation with a terminal deletion in r (11) and these findings provide important information for genetic counseling for this family, and may improve the understanding of the genotype-phenotype correlation of ring chromosome 11 disorders.
Abstract: Background
Ring chromosome 11[r (11)] is a rare chromosomal abnormality that forms when both arms of chromosome 11 break, and then reunite with each other. Once a ring chromosome forms, the distal ends of both arms of the chromosome are usually lost.
TL;DR: The results indicate that ring chromosome 21 is a rare, but recurrent chromosomal abnormality in male factor infertility and defective spermatogenesis is not associated with the deletion of any gene or genes located in the subtelomeric region of chromosome 21.
Abstract: In this report, we describe a patient with azoospermia in conjection with de novo ring chromosome 21 and monosomy 21 mosaicism. Inter-phase fluorescence in situ hybridisation (FISH) studies on uncultured peripheral blood and epithelial cells obtained by buccal smear revealed that 25% of the uncultured blood cells and 11% of the epithelial cells were monosomic for chromosome 21. Y chromosome microdeletion analysis ruled out the presence of any genomic deletions in the azoospermic factor a,b,c regions on the long arm of chromosome Y. Additionally, through subtelomeric FISH analysis, it was found that there was no deletion in the subtelomeric region of ring chromosome 21. Our results indicate that ring chromosome 21 is a rare, but recurrent chromosomal abnormality in male factor infertility. Furthermore, in individuals with ring chromosome 21, defective spermatogenesis is not associated with the deletion of any gene or genes located in the subtelomeric region of chromosome 21.
TL;DR: The first postnatal diagnosis of a child from Central Brazil with de novo cytogenetic alterations in 13q showing malformations of the brain, eyes, distal limbs, and genitourinary tract, and severe intellectual disability is described.
Abstract: We describe the first postnatal diagnosis of a child from Central Brazil with de novo cytogenetic alterations in 13q showing malformations of the brain, eyes, distal limbs, and genitourinary tract, and severe intellectual disability. The karyotype was a constitutive 46,XX,r(13)[77]/45,XX,-13[17]/46,XX,idic r(13)[6]. Interphase and metaphase fluorescence in situ hybridization analyses also showed the absence of 13qter and the presence of 13q14.3 in the cells with r(13), and chromosome microarray analysis detected a 15.39 Mb deletion in chromosome region 13q32.3-q34. This study is intended as the registry of a rare case of chromosomal rearrangement involving chromosome 13 in Central Brazil. Further studies are needed to define whether genetic haploinsufficiency is associated with each major 13q deletion anomaly.
TL;DR: It is demonstrated that whole-genome low-coverage paired-end NGS can be used directly to map breakpoints with a high molecular resolution and detect all CNVs on r(18), which will provide new insights into the genotype-phenotype correlations on r (18) and the underlying mechanism of ring chromosomes formation.
Abstract: Ring chromosomes are one category of structurally abnormal chromosomes that can lead to severe growth retardation and other clinical defects. Traditionally, their diagnosis and characterization has largely relied on conventional cytogenetics and fluorescence in situ hybridization, array-based comparative genomic hybridization and single nucleotide polymorphism array-based comparative genomic hybridization. However, these methods are ineffectively at characterizing the ring chromosome structure and only offer a low resolution mapping of breakpoints. Here, we applied whole-genome low-coverage paired-end next generation sequencing (NGS) to two suspected cases of ring chromosome 18 (r(18)) and characterized the ring structure including the chromosome dosage changes and the breakpoint junction. The breakpoints and chromosome copy number variations (CNVs) of r(18) were characterized by whole-genome low-coverage paired-end NGS. We confirmed the dosage change by single nucleotide polymorphisms array, and validated the junction site regions using PCR followed by Sanger sequencing. We successfully and fully characterized the r(18) in two cases by NGS. We mapped the breakpoints with a high resolution and identified all CNVs in both cases. We analyzed the breakpoint regions and discovered two breakpoints located within repetitive sequence regions, and two near the repetitive sequence regions. One of the breakpoints in case 2 was located within the gene METTL4, while the other breakpoints were intergenic. We demonstrated that whole-genome low-coverage paired-end NGS can be used directly to map breakpoints with a high molecular resolution and detect all CNVs on r(18). This approach will provide new insights into the genotype-phenotype correlations on r(18) and the underlying mechanism of ring chromosomes formation. Our results also demonstrate that this can be a powerful approach for the diagnosis and characterization of ring chromosomes in the clinic.
TL;DR: This is the first patient carrying a mosaic neocentric SRC derived from the long arm of chromosome 7.1q31 present in low mosaic and contributes to the delineation of the partial trisomy 7q phenotype.
Abstract: Supernumerary ring chromosomes (SRC) are usually derived from regions adjacent to the centromere. Their identification may be challenging, particularly in case of low mosaicism. Here, we report on a patient who was referred for major in utero growth retardation, severe developmental delay, facial dysmorphism, cleft palate, and hypospadias. The karyotype showed a small SRC in mosaic. The combination of FISH, M-FISH and array-CGH was necessary for a complete characterization of this SRC. M-FISH revealed that the SRC originated from chromosome 7. Array-CGH performed with a 400K oligonucleotide array showed a gain in region 7q22.1q31.1 present in low mosaic. This result was confirmed by FISH using BAC probes specific for chromosome 7. The SRC was a neocentric ring derived from 7q22.1q31.1 and was found in only 8% of the cells. This is the first patient carrying a mosaic neocentric SRC derived from the long arm of chromosome 7. Our study emphasizes the need to combine different techniques and to use adapted bioinformatic tools for low-mosaicism marker identification. It also contributes to the delineation of the partial trisomy 7q phenotype.
TL;DR: In this study, cytogenetic effects of 99technetium (99Tc) on meristematic cells of root tips belonging to Vicia faba L. have been investigated and abnormalities usually increased with increased treatment time.
Abstract: In this study, cytogenetic effects of 99technetium (99Tc) on meristematic cells of root tips belonging to Vicia faba L. have been investigated. Seeds of the plant were prepared and kept in 99Tc standard for different time periods: 1/12, 1/4, 1/2, 1, 2, 3, 4, 5, 6 and 12 h. Seeds treated with 99Tc were sprouted and the root tips obtained were prepared for microscopic examination. Some abnormalities e.g. chromosome breaking, chromosome dispersion, bridge chromosomes, chromosome adherence and ring chromosomes were observed. Abnormalities seen for each treatment depended on the time period. The variety and number of abnormalities usually increased with increased treatment time. The results obtained were evaluated statistically.
TL;DR: The first case of a girl with ring chromosome 17 and a normal neurological and general cognitive profile is reported, and the clinical and epilepsy phenotype was, to a certain degree, similar to that of ring 20 syndrome.
Abstract: Ring chromosomes are rare abnormalities caused by the fusion of the telomeric regions. Three-ring chromosome syndromes (Cr 20, Cr 17 and Cr 14) cause epilepsy with variable phenotypes. In ring 17 patients with mild phenotype, some authors have shown an epilepsy syndrome similar to that of ring 20. We report the first case of a girl with ring chromosome 17 and a normal neurological and general cognitive profile. She had had, from 9 years old, focal pharmacoresistant epilepsy associated with episodes of non-convulsive status epilepticus with mainly autonomic features. Cytogenetic analysis revealed an abnormal karyotype characterised by the presence of de novo ring chromosome 17 in 19% of metaphases. The array CGH (100 KB) did not show any genetic deletion. The clinical and epilepsy phenotype was, to a certain degree, similar to that of ring 20 syndrome.
TL;DR: A case with a very rarely reported class II neocentromere formation in an aberrant chromosome 7 is presented, and analysis revealed that the linear acentric fragment was part of the 7q region, which suggests that there could be a possible McClintock mechanism.
Abstract: A neocentromere is a functional centromere that has arisen within a region not known to have a centromere. We present a case with a very rarely reported class II neocentromere formation in an aberrant chromosome 7. A 22-month-old male was referred because of dysmorphic features. Banding cytogenetics was performed, and a ring 7 and a supernumerary marker chromosome along with a normal chromosome 7 were found. In situ hybridization using a centromeric probe revealed 46 signals, of which 2 signals for chromosome 7 were observed, one on the normal and one on the ring chromosome. Further analysis using FISH revealed that the linear acentric fragment was part of the 7q region, which suggests that there could be a possible McClintock mechanism.
TL;DR: It is speculated that gene(s) located on chromosome 11 might be involved in the pathogenesis of these conditions and studies to correlate the genes located on the chromosomes with the phenotypes observed could lead to major advances in the understanding and treatment of more prevalent diseases.
Abstract: Ring chromosomes (RCs) are uncommon cytogenetic findings, and RC11 has only been described in 19 cases in the literature. Endocrine abnormalities associated with RC11 were reported for two of these cases. The clinical features of RC11 can result from an alteration in the structure of the genetic material, ring instability, mosaicism, and various extents of genetic material loss. We herein describe a case of RC11 with clinical features of 11q-syndrome and endocrine abnormalities that have not yet been reported. A 20-year-old female patient had facial dysmorphism, short stature, psychomotor developmental delays, a ventricular septal defect, and thrombocytopenia. Karyotyping demonstrated RC11 (46,XX,r(11)(p15q25)). This patient presented with clinical features that may be related to Jacobsen syndrome, which is caused by partial deletion of the long arm of chromosome 11. Regarding endocrine abnormalities, our patient presented with precocious puberty followed by severe hirsutism, androgenic alopecia, clitoromegaly, and amenorrhea, which were associated with overweight, type 2 diabetes mellitus (T2DM), and hyperinsulinemia; therefore, this case meets the diagnostic criteria for polycystic ovary syndrome. Endocrine abnormalities are rare in patients with RC11, and the association of RC11 with precocious puberty, severe clinical hyperandrogenism, insulin resistance, and T2DM has not been reported previously. We speculate that gene(s) located on chromosome 11 might be involved in the pathogenesis of these conditions. Despite the rarity of RCs, studies to correlate the genes located on the chromosomes with the phenotypes observed could lead to major advances in the understanding and treatment of more prevalent diseases.
Learning points
We hypothesize that the endocrine features of precocious puberty, severe clinical hyperandrogenism, insulin resistance, and T2DM might be associated with 11q-syndrome.
A karyotype study should be performed in patients with short stature and facial dysmorphism.
Early diagnosis and adequate management of these endocrine abnormalities are essential to improve the quality of life of the patient and to prevent other chronic diseases, such as diabetes and its complications.
TL;DR: This work reconsidered the ring chromosome 2 case previously published by Côté et al.
Abstract: Cote et al. [1981] suggested that ring chromosomes with or without deletions share a common pattern of phenotypic anomalies, regardless of which chromosome is involved. The phenotype of this 'general ring syndrome' consists of growth failure without malformations, few or no minor anomalies, and mild to moderate mental retardation. We reconsidered the ring chromosome 2 case previously published by Cote et al. [1981], and we characterized it by array CGH, polymorphic markers as well as subtelomere MLPA and FISH analysis. A terminal deletion (q37.3qter) of maternal origin of the long arm of the ring chromosome 2 was detected and confirmed by all the above-mentioned methods. Ring chromosome 2 cases are exceedingly rare. Only 18 cases, including the present one, have been published so far, and our patient is the longest reported survivor, with a 35-year follow-up, and the third case characterized by array-CGH analysis.
01 Jul 2015
TL;DR: A case of a derivative chromosome 7 formed by a ring chromosome 7 and t(7;9) was found who presented with dimorphic anaemia with no other anomaly.
Abstract: A case of a derivative chromosome 7 formed by a ring chromosome 7 and t(7;9) was found who presented with dimorphic anaemia with no other anomaly. Ring chromosome 7 was characterized by conventional and molecular cytogenetic techniques.
TL;DR: The presence of a trisomic cell line and absence of isodisomy of chromosome 21 support trisomy rescue as a plausible mechanism for mosaicism and the complex mosaic karyotype as the likely cause of down syndrome.
Journal Article•
TL;DR: A ring chromosome aberration added to the spectrum of both morphology and genetic rearrangements in oncology malignancies and diagnosed as accelerated CML.
Abstract: UNLABELLED Ring chromosome aberration are rare abnormality potentially involving any chromosome in patients diagnosing in Oncology. The present review and case study has focused on the ring chromosome associated with oncology malignancies. MATERIAL AND METHODS An electronic peer review article search was performed systematically to obtain relevant literature with the CINAHL, Google scholar, and Pub Med databases. The keywords included marker, abnormalities, structural, Ring chromosome. The inclusion criteria for the review were that the documents were original quantitative research and published in English. This was also initiated using Medline, Mitelman database (http://cgap.nci.nih.gov/Chromosomes/Mitelman), Danish cytogenetic register and other pertinent web references on ring chromosomes in Oncology malignancies. Articles that were not directly relevant to the present objective were excluded. Also the un-stimulated bone marrow specimen of present case manipulated with Methotrexate cells culture synchronization and finally was treated by GTGbanding technique. RESULTS Ring chromosome was observed in 10% of the total cells. Cytogenetic analysis demonstrated apparently ring (15) 46, XY, r(15) karyotype. The clinical findings revealed history of nausea, loss of appetite, diarrhea, night sweats, and a weight loss, anemia and diagnosed as accelerated CML. CONCLUSION Our finding adds to the spectrum of both morphology and genetic rearrangements in oncology malignancies. Additional future analyses in similar subject will be necessary to draw firm conclusions.
01 Jan 2015
TL;DR: A black female African with malformation and a mixture of major features in ring 9 and deletion of the short arm of chromosome 9 syndrome characteristics upon ring shape by one of chromosomes 9 at cytogenetic evaluation is reported here.
Abstract: Ring 9 Chromosome Syndrome in Black African Infant
Ring chromosomes are rare entities, usually associated with phenotypic abnormalities in correlation with the loss of genetic material. Ring 9 chromosome syndrome is very rare. The majority of reported cases revealed a less distinct clinical picture of shortness of stature, microcephaly and mental retardation. A minority had the clinical pattern of patients with the deletion of the short arm of chromosome 9 syndrome. We reported here a black female African with malformation and a mixture of major features in ring 9 and deletion of the short arm of chromosome 9 syndrome characteristics upon ring shape by one of chromosome 9 at cytogenetic evaluation.
Journal Article•
TL;DR: The second male patient found with azoospermia in conjunction with mosaicism for 45,X karyotype and ring Y chromosome without AZFa,b,and c deletions is described.
Abstract: Infertility is an important health problem which affects aproximately 10-15% of couples and, in 30-50% of these couples, infertility is due to male factor infertility (1). Recently, Hoffher et al. (4) performed a meta-analysis by reviewing previously published reports in the literature to determine the cumulative frequencies of chromosomal abnormalities and chromosome Y microdeletions in infertile males. According to their results, the 47,XXY karyotype, which is associated with both Klinefelter syndrome and its variants, were found to be the most frequent chromosomal abnormalities, with a frequency of 4.9%, followed by autosomal chromosome abnormalities (3.5%) and structural sex chromosomal abnormalities (1.8%). Furthermore, they estimated that the frequency of Y chromosome microdeletions in infertile males was 3.5% (4). To the best of our knowledge, there have been only thirteen cases reported in the literature in which male factor infertility was found in association with a ring Y chromosome, and in only two of these cases was the male factor infertility not associated with loss of AZFa,b,c regions located at Yql 1.2. While one of these two cases had oligoasthenospermia, the other had azoospermia.Here, we describe the second male patient found with azoospermia in conjunction with mosaicism for 45,X karyotype and ring Y chromosome without AZFa,b,and c deletions.A 29-years old man was admitted to our clinic due to male factor infertility. Neither his previous medical nor family history contained any information of relevance to his case. On physical examination, both testes were soft and 12 cc in size. The ductus deferens was palpable and normal in shape, bilaterally, and there wasn't any sign of varicocele on either side. Analysis of the patient's semen was performed on 2 different occasions and revealed complete azoospermia. The patient's hormone profile was found to be as follows: luteinizing hormone levels were 3.580 mIU/ml (1.70-8.60 mIU/ml), the follicle stimulating hormone levels were 2.760 mIU/ml (1.50-12.40 mIU/ml), and total testosterone and free testosterone levels were 2.630 ng/ml (2.808.00ng/ml) and 10.050 pg/mL (8.90-42.50 pg/mL), respectively. As is standard procedure with men found to have azoospermia, the patient was referred to the medical genetic diagnostic laboratory for both chromosomal karyotyping and Y chromosome microdeletion analysis.Conventional cytogenetic analysis of the patient's peripheral blood lymphocytes revealed a ring chromosome Y (Fig. la). C-banding showed that ring chromosome Y was monocentric and did not contain a constitutional heterochromatin region located in the Yql2 band (Fig. lb). Therefore, the breakpoint on the long arm of chromosome Y was thought to be Yqll.2. The karyotype of the father was found to be normal. FISH analysis showed that the SRY located in the Ypl 1.2 and centromeric alfa satellite DNA was intact on ring chromosome Y (Fig. lc-d). Based on the FISH analysis, the patient's final karyotype was designated as: 45,X[ 10]/46,X,dic r(Y)(pll.2.qll.2)[4]/46,X,r(Y) (pll.2.qll.2)[86], ish r(Y)(pll.2qll.2) (SRY+, DYZ3+, DYZ1-). Y chromosome microdeletion analysis showed that the patient did not have any genomic deletions in the AZFa, AZFb and AZFc regions on the long arm of the Y chromosome.There are only six previous reports in the literature of infertile males that had a ring Y chromosome with AZF deletions that had been studied (2, 3, 5, 6) (Table I). As with our case, five of these patients had azoospermia, whereas one case had oligoastenospermia. Five cases had varying degrees of mosaicism for 45,X and 46,X,r(Y) cell lines. …
TL;DR: Molecular cytogenetic investigation using fluorescence in situ hybridization method allowed us to characterize the markers including the Prader-Willi syndrome locus that contains the small nuclear ribonucleoprotein polypeptide N (SNRPN) gene, and Tetrasomy and trisomy for the 15q11-q13 chromosomal region were found in the first and the second patient.
Abstract: In this study, we report two patients with the supernumerary marker chromosome (15)s. The first case is an 8.5-year-old girl with an inv dup (15) syndrome, mental retardation and dysmorphic features. The second case is a 13-year-old boy with a ring chromosome 15, who was referred to the Laboratory of Cytogenetic and Biology of Reproduction in Sousse, Tunisia for mental retardation, epilepsy, speech delay, hypotonia and other mild dysmorphic features. R banding showed the presence of a marker chromosome in both cases. Molecular cytogenetic investigation using fluorescence in situ hybridization method allowed us to characterize the markers including the Prader-Willi syndrome locus that contains the small nuclear ribonucleoprotein polypeptide N (SNRPN) gene. Tetrasomy and trisomy for the 15q11-q13 chromosomal region were found in the first and the second patient, respectively. This observation reinforces the hypothesis that additional copies of proximal chromosome 15q11 segment may be causally related to mental retardation and dysmorphic features.
TL;DR: The physical examination at 6 years and 1 month old has shown a female, Caucasian, born in Southeast of Brazil, 6 years old with a normal karyotype, and the clinical presentation of ring chromosome 13 with the extension of the deleted chromosomal region and instability.
Abstract: Aims: To report a case of ring chromosome 13 in a female child. Presentation of Case: Female, Caucasian, born in Southeast of Brazil, 6 years old. Born by cesarean section, the physical examination at 6 years and 1 month old has shown: weight of 19.100 grams and 105 centimeters tall, developmental delay, bushy eyebrows, epicanthic folds and broad nasal bridge, cardiovascular and respiratory systems were normal and no abnormalities in the limbs. Chromosome analysis was performed by GTG banding of peripheral blood and the karyotype was 46,XX,r(13)(p13q34)[97]/46,XX,dic r(13;13)(p13q34;p13q34) [3]. Analysis of 100 metaphases following G-banding revealed 97% cells with a ring chromosome 13,3% with dicentric ring chromosome of two 13s. Aneuploidy was not detected. Her parents had a normal karyotype. Discussion: Some researchers relate the clinical presentation of ring chromosome 13 with the extension of the deleted chromosomal region and instability. Others suggested that phenotypes of