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Chromosome Abnormalities (chromosome + abnormality)
Selected AbstractsChromosome 18 suppresses tumorigenic properties of human prostate cancer cellsGENES, CHROMOSOMES AND CANCER, Issue 3 2006Audrey Gagnon Although prostate cancer is still the most diagnosed cancer in men, most genes implicated in its progression are yet to be identified. Chromosome abnormalities have been detected in human prostate tumors, many of them associated with prostate cancer progression. Indeed, alterations (including deletions or amplifications) of more than 15 human chromosomes have been reported in prostate cancer. We hypothesized that transferring normal human chromosomes into human prostate cancer cells would interfere with their tumorigenic and/or metastatic properties. We used microcell-mediated chromosome transfer to introduce human chromosomes 10, 12, 17, and 18 into highly tumorigenic (PC-3M-Pro4) and highly metastatic (PC-3M-LN4) PC-3-derived cell lines. We tested the in vitro and in vivo properties of these hybrids. Introducing chromosome 18 into the PC-3M-LN4 prostate cancer cell line greatly reduced its tumorigenic phenotype. We observed retarded growth in soft agar, decreased invasiveness through Matrigel, and delayed tumor growth into nude mice, both subcutaneously and orthotopically. This phenotype is associated with a marker in the 18q21 region. Combined with the loss of human chromosome 18 regions often seen in patients with advanced prostate cancer, our results show that chromosome 18 encodes one or more tumor-suppressor genes whose inactivation contributes to prostate cancer progression. © 2005 Wiley-Liss, Inc. [source] Characterization of 6q abnormalities in childhood acute myeloid leukemia and identification of a novel t(6;11)(q24.1;p15.5) resulting in a NUP98,C6orf80 fusion in a case of acute megakaryoblastic leukemiaGENES, CHROMOSOMES AND CANCER, Issue 3 2005Sabrina Tosi Chromosome abnormalities of 6q are not frequently observed in myeloid disorders. In this article, we report the incidence of these chromosome changes in childhood myeloid leukemia as 2%,4% based on the cytogenetic database of a single institution. We applied fluorescence in situ hybridization (FISH) to characterize precisely the types of 6q abnormalities in seven patients (six with acute myeloid leukemia and one with myelodysplastic syndrome). They carried various translocations involving different breakpoints in 6q, as confirmed by FISH using a whole-chromosome-6 paint. Four cases were reported as t(6;11), although the breakpoints varied. Among these, we identified a novel translocation, t(6;11)(q24.1;p15.5), in a patient with acute megakaryoblastic leukemia. Molecular cytogenetic studies using the PAC clone RP5-1173K1 localized the genomic breakpoint on chromosome 11 to within the NUP98 gene. The breakpoint on chromosome 6 was narrowed down to a 500-kb region between BAC clones RP11-721P14 and RP11-39H10. Reverse-transcription PCR was performed using a forward primer specific for NUP98 and a reverse primer for the candidate gene in the 500-kb interval in 6q. This experiment resulted in the identification of a new fusion between NUP98 and C6orf80. Further studies will aim to fully characterize C6orf80 and will elucidate the role of this new NUP98 fusion in myeloid leukemia. © 2005 Wiley-Liss, Inc. [source] Aberrant increase in the immature platelet fraction in patients with myelodysplastic syndrome: a marker of karyotypic abnormalities associated with poor prognosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Naomi Sugimori Abstract Objectives:, Some patients with myelodysplastic syndrome (MDS) show a marked increase in the percentage of immature platelet fraction (IPF%) despite the absence of severe thrombocytopenia. To determine the significance of such an unbalanced increase in the IPF%, we investigated the IPF% and other laboratory findings of 51 patients recently diagnosed with MDS. Method:, Subjects consisted of 80 healthy males, 90 healthy females, and 51 patients with MDS and 20 patients with idiopathic thrombocytopenic purpura (ITP). The IPF and IPF% were determined using a Sysmex XE-2100 system loaded with IPF Master software (XE IPF Master, Sysmex). Platelet counts were measured simultaneously. Results:, IPF% and platelet counts of these patients ranged from 1.1% to 25.1% (median, 5.3%) and from 6 to 260 × 109/L (median, 71 × 109/L), respectively. Twelve patients showed platelet counts more than 50 × 109/L with 10% or more IPF%. All of the 12 patients had chromosome abnormalities including monosomy 7 and complex abnormalities involving 7 or 5q. In the other 39 patients who did not show the aberrant IPF% increase, chromosomal abnormalities were seen only in seven patients and none of them had chromosome 7 abnormalities. The IPF% of two patients increased to more than 10% in association with the appearance of monosomy 7. Conclusions:, These findings suggest that a high IPF% in MDS patient may be a marker for karyotypic abnormalities with a poor prognosis, including chromosome 7 abnormalities. [source] Definitive molecular cytogenetic characterization of 15 colorectal cancer cell lines,GENES, CHROMOSOMES AND CANCER, Issue 3 2010Turid Knutsen In defining the genetic profiles in cancer, cytogenetically aberrant cell lines derived from primary tumors are important tools for the study of carcinogenesis. Here, we present the results of a comprehensive investigation of 15 established colorectal cancer cell lines using spectral karyotyping (SKY), fluorescence in situ hybridization, and comparative genomic hybridization (CGH). Detailed karyotypic analysis by SKY on five of the lines (P53HCT116, T84, NCI-H508, NCI-H716, and SK-CO-1) is described here for the first time. The five lines with karyotypes in the diploid range and that are characterized by defects in DNA mismatch repair had a mean of 4.8 chromosomal abnormalities per line, whereas the 10 aneuploid lines exhibited complex karyotypes and a mean of 30 chromosomal abnormalities. Of the 150 clonal translocations, only eight were balanced and none were recurrent among the lines. We also reviewed the karyotypes of 345 cases of adenocarcinoma of the large intestine listed in the Mitelman Database of Chromosome Aberrations in Cancer. The types of abnormalities observed in the cell lines reflected those seen in primary tumors: there were no recurrent translocations in either tumors or cell lines; isochromosomes were the most common recurrent abnormalities; and breakpoints occurred most frequently at the centromeric/pericentromeric and telomere regions. Of the genomic imbalances detected by array CGH, 87% correlated with chromosome aberrations observed in the SKY studies. The fact that chromosome abnormalities predominantly result in copy number changes rather than specific chromosome or gene fusions suggests that this may be the major mechanism leading to carcinogenesis in colorectal cancer. Published 2009 Wiley-Liss, Inc. [source] Data management and statistical methods used in the analysis of balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and therapy-related acute leukemia: Report from an International Workshop,GENES, CHROMOSOMES AND CANCER, Issue 4 2002Theodore Karrison First page of article [source] Detection of unidentified chromosome abnormalities in human neuroblastoma by spectral karyotyping (SKY)GENES, CHROMOSOMES AND CANCER, Issue 3 2001Ninette Cohen Spectral karyotyping (SKY) is a novel technique based on the simultaneous hybridization of 24 fluorescently labeled chromosome painting probes. It provides a valuable addition to the investigation of many tumors that can be difficult to define by conventional banding techniques. One such tumor is neuroblastoma, which is often characterized by poor chromosome morphology and complex karyotypes. Ten primary neuroblastoma tumor samples initially analyzed by G-banding were analyzed by SKY. In 8/10 tumors, we were able to obtain additional cytogenetic information. This included the identification of complex rearrangements and material of previously unknown origin. Structurally rearranged chromosomes can be identified even in highly condensed metaphase chromosomes. Following the SKY results, the G-banding findings were reevaluated, and the combination of the two techniques resulted in a more accurate karyotype. This combination allows identification not only of material gained and lost, but also of breakpoints and chromosomal associations. The use of SKY is therefore a powerful tool in the genetic characterization of neuroblastoma and can contribute to a better understanding of the molecular events associated with this tumor. © 2001 Wiley-Liss, Inc. [source] Integration of amplified BCR/ABL fusion genes into the short arm of chromosome 17 as a novel mechanism of disease progression in chronic myeloid leukemiaGENES, CHROMOSOMES AND CANCER, Issue 1 2001Simone Metzke-Heidemann We describe the cases of two patients with Philadelphia chromosome,positive chronic myeloid leukemia (CML), in whom the extramedullary blastic phase developed during disease progression. The similar clinical presentations of these patients was accompanied by gain of identical secondary chromosome abnormalities, that is, monosomies 9, 14, and 22, and by a clustered amplification of the BCR/ABL fusion gene. The additional copies of the BCR/ABL fusion gene were integrated into the short arm of structurally abnormal chromosomes 17 in both patients. The conformity of these genetic features in two patients with a rare disease manifestation leads us to the assumption that either the clustered amplification of the BCR/ABL fusion gene or the integration of this cluster into the short arm of chromosome 17 or both are associated with extramedullar disease progression in CML. Furthermore, the insertion of amplified BCR/ABL fusion genes into structurally abnormal chromosomes provides a novel mechanism of disease progression in BCR/ABL -positive CML. © 2001 Wiley-Liss, Inc. [source] Role of X chromosome defects in primary biliary cirrhosisHEPATOLOGY RESEARCH, Issue 2007Pietro Invernizzi Similar to the majority of autoimmune conditions, primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by a striking female predominance; it is characterized by high titer serum autoantibodies to mitochondrial antigens, elevated serum immunoglobulin M, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. Familiarity and high concordance rates for the disease among monozygotic twins strongly support the role of genetics in the disease. Experimental efforts have been dedicated by our and other research groups to investigate the role of X chromosome abnormalities (i.e. monosomyrates and inactivation patterns) in autoimmunity. Our recent work has demonstrated enhanced X monosomy in women with PBC as well as two other female-predominant autoimmune diseases, systemic sclerosis and autoimmune thyroid disease. We will review herein the most recent evidence on the role of the X chromosome in PBC onset and discuss the potential implications. Future developments of these findings will be discussed. [source] Aneuploidy in spermatozoa of infertile men with teratozoospermiaINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2001Kati HÄrkönen Recent studies have shown that aneuploidy in spermatozoa of infertile men with poor semen quality is increased. The purpose of this study was to determine whether poor sperm morphology is associated with the incidence of spermatozoa with numerical chromosome abnormalities. Semen samples from 20 infertile teratozoospermic men were studied using multicolour fluorescence in situ hybridization (FISH). Men were divided into four groups according to the proportion of normal sperm morphology: infertile men with <10% (group A, n=7), 10,19% (group B, n=6), and 20,29% (group C, n=7) of morphologically normal spermatozoa, and controls (group D, n=5) with ,30% normal forms. Two hybridizations were performed. All the samples were analysed using probes for chromosomes 1 and 7 and, in addition, in group A and in controls with normal semen parameters probes for chromosomes X, Y and 18 were also used. Ten thousand spermatozoa were scored per hybridization. Severely teratozoospermic men (<10% normal forms) had significantly higher frequency of disomy 7, 18, YY, XY and diploidy in their spermatozoa when compared with controls. The results suggest that poor sperm morphology is associated with numerical chromosome abnormalities of spermatozoa. Severely teratozoospermic men may be at an increased risk of producing aneuploid offspring. [source] Unbalanced expression of licensing DNA replication factors occurs in a subset of mantle cell lymphomas with genomic instabilityINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Magda Pinyol Abstract DNA licensing is a crucial process for chromosome replication control. Deregulation of the licensing factors Cdt1, Cdc6 and the licensing inhibitor geminin has been associated with DNA replication defects and chromosomal instability. We examined the expression of these factors, in mantle cell lymphoma (MCL) and non-neoplastic lymphoid samples, and analysed the potential role of their deregulation in genomic instability. Geminin, Cdt1 and Cdc6 were coordinately expressed in non-neoplastic tissues and most MCL in relationship to the proliferative activity of the cells. However, 6 (18%) tumours showed an unbalanced "licensing signature" characterized by a higher expression of Cdt1 and Cdc6 than the negative regulator geminin. Tumours with this unbalanced signature and p53/p14ARF alterations had significantly higher number of chromosome abnormalities than lymphomas with p53/p14ARF alterations but with a normal licensing signature. No aberrations of Cdct1, Cdc6, and geminin genes were detected in cases with unbalanced licensing. However, tumours with p53/ARF inactivation and unbalanced licensing signature had significantly higher cyclin D1 levels than tumours with normal licensing signature. These results suggest that an unbalanced mRNA expression of licensing regulatory genes may play a role in the pathogenesis of the chromosomal instability of a subset of MCL with inactivation of the p53/p14ARF pathway. © 2006 Wiley-Liss, Inc. [source] Further characterization of human fetal osteoblastic hFOB 1.19 and hFOB/ER, cells: Bone formation in vivo and karyotype analysis using multicolor fluorescent in situ hybridizationJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2002M. Subramaniam Abstract We have previously generated an immortalized human fetal osteoblastic cell line (hFOB) using stably transfected temperature sensitive SV40 T-antigen (Harris et al. [1995a] J. Bone. Miner. Res. 10:178,1860). To characterize these cells for phenotypic/genotypic attributes desired for a good cell model system, we performed karyotype analysis by multicolor fluorescent in situ hybridization (M-FISH), their ability to form bone in vivo without developing cell transformation, and finally their ability to form extracellular matrix formation in vitro. The karyotype analysis of hFOB cells revealed structural or numeric anomalies involving 1,2 chromosomes. In contrast, the human osteosarcoma MG63 cells displayed multiple, and often complex, numeric, and structural abnormalities. Subcutaneous injection of hFOB cells in the presence of Matrigel into nude mice resulted in bone formation after 2,3 weeks. Electron microscopic analysis of the extracellular matrix deposited by hFOB cells in culture revealed a parallel array of lightly banded fibrils typical of the fibrillar collagens such as type I and III. These results demonstrate that the hFOB cell line has minimal chromosome abnormalities, exhibit the matrix synthetic properties of differentiated osteoblasts, and are immortalized but non-transformed cell line. These hFOB cells thus appear to be an excellent model system for the study of osteoblast biology in vitro. J. Cell. Biochem. 87: 9,15, 2002. © 2002 Wiley-Liss, Inc. [source] Combined BubR1 protein down-regulation and RASSF1A hypermethylation in Wilms tumors with diverse cytogenetic changesMOLECULAR CARCINOGENESIS, Issue 9 2008Masayuki Haruta Abstract BUB1B and RASSF1A genes play specific roles in the mitotic checkpoint, and their defects may cause chromosome instability or aneuploidy in mouse fibroblasts and human cancer cell lines; however, few studies have reported a correlation between defects in these genes and chromosome changes in human tumor samples. We examined chromosome abnormalities in 25 Wilms tumors by metaphase comparative genomic hybridization, and classified them into 14 hyperdiploid (50,,,chromosomes), 2 near-or-pseudodiploid, and 9 diploid tumors. We also examined various molecular aspects of BUB1B and RASSF1A, and evaluated the relationship between chromosome changes and the status of both genes. No tumors showed BUB1B mutation. BubR1 protein (BUB1B gene product) expression was undetectable or decreased in five of six hyperdiploid or near-or-pseudodiploid tumors and increased in four of five diploid tumors, whereas all seven tumors examined showed BUB1B mRNA expression irrespective of their chromosome pattern. Furthermore, while complete promoter methylation of RASSF1A was found in 13 of 16 hyperdiploid or near-or-pseudodiploid tumors, unmethylated RASSF1A was found in 5 of 9 diploid tumors. Partial RASSF1A methylation was found in three hyperdiploid or near-or-pseudodiploid tumors and in four diploid tumors. Thus, BubR1 protein expression decreased, and the promoter region of RASSF1A was completely methylated in the great majority of hyperdiploid or near-or-pseudodiploid tumors, BubR1 protein expression increased and RASSF1A was unmethylated in the majority of diploid tumors. These findings suggest that the combined BubR1 protein down-regulation and RASSF1A hypermethylation might be implicated in the formation of chromosomal changes found in Wilms tumors. © 2008 Wiley-Liss, Inc. [source] Numerical chromosomal abnormalities in equine embryos produced in vivo and in vitroMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2005B.P.B. Rambags Chromosomal aberrations are often listed as a significant cause of early embryonic death in the mare, despite the absence of any concrete evidence for their involvement. The current study aimed to validate fluorescent in situ hybridization (FISH) probes to label specific equine chromosomes (ECA2 and ECA4) in interphase nuclei and thereby determine whether numerical chromosome abnormalities occur in horse embryos produced either in vivo (n,=,22) or in vitro (IVP: n,=,20). Overall, 75% of 36,720 and 88% of 2,978 nuclei in the in vivo developed and IVP embryos were analyzable. Using a scoring system in which extra FISH signals were taken to indicate increases in ploidy and "missing" signals were assumed to be "false negatives," 98% of the cells were scored as diploid and the majority of embryos (30/42: 71%) were classified as exclusively diploid. However, one IVP embryo was recorded as entirely triploid and a further seven IVP and four in vivo embryos were classified as mosaics containing diploid and polyploid cells, such that the incidence of apparently mixoploid embryos tended to be higher for IVP than in vivo embryos (P,=,0.118). When the number of FISH signals per nucleus was examined in more detail for 11 of the embryos, the classification as diploid or polyploid was largely supported because 2,174 of 2,274 nuclei (95.6%) contained equal numbers of signals for the two chromosomes. However, the remaining 100 cells (4.4%) had an uneven number of chromosomes and, while it is probable that many were artefacts of the FISH procedure, it is also likely that a proportion were the result of other types of aneuploidy (e.g., trisomy, monosomy, or nullisomy). These results demonstrate that chromosomally abnormal cells are present in morphologically normal equine conceptuses and suggest that IVP may increase their likelihood. Definitive distinction between polyploidy, aneuploidy and FISH artefacts would require the use of more than one probe per chromosome and/or probes for more than two chromosomes. © 2005 Wiley-Liss, Inc. [source] Holoprosencephaly due to numeric chromosome abnormalities,,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Benjamin D. Solomon§ Abstract Holoprosencephaly (HPE) is the most common malformation of the human forebrain. When a clinician identifies a patient with HPE, a routine chromosome analysis is often the first genetic test sent for laboratory analysis in order to assess for a structural or numerical chromosome anomaly. An abnormality of chromosome number is overall the most frequently identified etiology in a patient with HPE. These abnormalities include trisomy 13, trisomy 18, and triploidy, though several others have been reported. Such chromosome number abnormalities are almost universally fatal early in gestation or in infancy. Clinical features of specific chromosome number abnormalities may be recognized by phenotypic manifestations in addition to the HPE. Published 2010 Wiley-Liss, Inc. [source] Comparison of microarray-based detection rates for cytogenetic abnormalities in prenatal and neonatal specimensPRENATAL DIAGNOSIS, Issue 9 2008Lisa G. Shaffer Abstract Objective To compare the detection rate by microarray analysis for chromosome abnormalities in a prenatal population to that of a neonatal population referred for diagnostic testing. Methods Array comparative genomic hybridization (aCGH) analysis was performed for 151 prenatal cases and compared with the results from 1375 postnatal cases less than 3 months of age. Results Two of 151 prenatal cases (1.3%) showed a clinically significant cytogenetic abnormality. In contrast, of the 1375 postnatal cases studied, 11.4% showed a cytogenetic abnormality by aCGH. Many of these (40%) were referred for aCGH because of dysmorphic features, a clinical indication unlikely to be identified in the prenatal population. Conclusions The chance of detecting a chromosome abnormality in a prenatal population that has already been screened by routine cytogenetics is ,1.3%. However, given that many of the abnormal array results in the neonatal population were among those with dysmorphic features as the primary indication for testing, which are not easily identifiable by ultrasound, offering prenatal testing by aCGH to a wider population would likely result in a higher detection rate. Copyright © 2008 John Wiley & Sons, Ltd. [source] Pregnancy outcome following prenatal diagnosis of sex chromosome abnormalities in Mainland ChinaPRENATAL DIAGNOSIS, Issue 5 2008Can Liao No abstract is available for this article. [source] A familial Xp+ chromosome detected during fetal karyotyping, which is associated with short stature in four generations of a Turkish familyPRENATAL DIAGNOSIS, Issue 4 2003B. Karaman Abstract The short-stature homeobox-containing gene (SHOX) on chromosome Xp22.3 was recently identified as an important determinant of the stature phenotype. Deletions of the SHOX gene, some of them due to structural chromosome abnormalities, have been described in patients with idiopathic short stature and Leri-Weill syndrome. Additionally, haploinsufficiency of SHOX is a main cause for short stature seen in patients with Turner syndrome. Here we report an unusual X-chromosome abnormality, which was detected during a fetal karyotyping performed because of a previous child with Down syndrome. GTG banding demonstrated an extra chromosome segment on the terminal part of the short arm of chromosome X in the index case (karyotype: 46,X,Xp+). The same chromosomal abnormality was found in the mother and the maternal grandmother. All carriers of this chromosomal abnormality presented with short stature but no other associated symptoms. Whole chromosome painting of X revealed a homogeneous painting of the abnormal X chromosome indicating that no other chromosome was involved. Additional FISH studies with probe DXS1140 (Kallmann probe at Xp22.3), Quint-Essential X-Specific DNA (DMD probe at Xp21.2), XIST (at Xq13.2), and Tel Xq/Yq were performed, and no abnormality was observed in the intensities or the localizations of the probes signals. However, applying a specific SHOX gene probe (derived from cosmid LLNONO3M34F5) showed a loss of signal on the derivative X chromosome. Our results show that the Xp+ generation led to a deletion of the complete SHOX gene and caused short stature in the presented family. Copyright © 2003 John Wiley & Sons, Ltd. [source] Preimplantation genetic diagnosis of pericentric inversionsPRENATAL DIAGNOSIS, Issue 9 2001Tomás Escudero Abstract Inversions are structural chromosome abnormalities that may be associated with infertility, multiple miscarriage and chromosomally unbalanced offspring. Preimplantation genetic diagnosis (PGD) with subtelomeric probes was used to select for transfer only those embryos that were normal or balanced for three pericentric inversions. In contrast to previous protocols the present procedure allows the detection of unbalanced embryos that might arise from U-recombination in the inverted region. Additionally, aneuploidy screening was carried out in two cases by a second round of fluorescent in situ hybridization (FISH) with centromeric probes. Of the three couples that underwent the procedure one became pregnant twice. The first pregnancy delivered a healthy and chromosomally normal baby and the second pregnancy is ongoing with triplets. Copyright © 2001 John Wiley & Sons, Ltd. [source] The selective use of rapid aneuploidy screening in prenatal diagnosisAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2009Jan E. DICKINSON Aims: To evaluate the diagnostic utility and costing of the selective use of rapid aneuploidy screening (RAS) for chorion villus sampling (CVS) and amniocentesis specimens. Methods: CVS and amniocenteses performed between 2000 and 2006 were identified. Cases were subdivided into two groups: (i) RAS in addition to long-term culture and (ii) long-term chromosome culture alone. The frequency of RAS, the proportion of abnormal results and the cytogenetic costings were reviewed. Results: A total of 3315 procedures were performed: 730 CVS and 2585 amniocenteses. An abnormal karyotype culture was present in 366 of 3315 (11%). For CVS an abnormal culture was present in 164 (22.5%). RAS (short-term culture/direct preparation) was selectively used in 399 cases (54.6%) with an abnormal result in 128 (32% of RAS). For amniocentesis, 206 chromosome abnormalities were present (8.0% of specimens). RAS (interphase FISH) was selectively used in 580 amniocenteses (22.4%). FISH was requested in 95 (66.4%) of the 143 abnormal cases potentially detectable with standard probes. There was a progressive increase in utilisation of RAS for amniocentesis (8.9% in 2000 to 43.3% of cases in 2006, P < 0.001). CVS RAS was stable. This liberalisation resulted in a fourfold increase in expenditure for FISH and cost/abnormality detected ($A970 per abnormal result in 2000 to $A4015 per abnormal result in 2006). Conclusion: The selective use of prenatal RAS results in a reasonably high detection rate for chromosomal anomalies. Liberalisation of RAS, however, is an expensive cytogenetic model. An approach based on some predictive level of risk combined with resource funding levels may be a more pragmatic approach. [source] Bipolar affective disorder in a male with a deletion of Y chromosome , a case reportBIPOLAR DISORDERS, Issue 3 2005Marcin Olajossy We report on a 25-year-old male with bipolar disorder, dysmorphic features and a deletion of the long arm of Y chromosome. A potential association between sex chromosome abnormalities and a susceptibility to major psychiatric disorders has been documented. However there have been very few reports on the coincidence of Y chromosome aberrations with bipolar disorder. Cytogenetic studies have contributed to the identification of several disease genes. Karyotyping of patients with bipolar disorder in order to identify candidate regions for linkage studies has been recommended. [source] Pai syndrome: First patient with agenesis of the corpus callosum and literature reviewBIRTH DEFECTS RESEARCH, Issue 10 2007Marco Castori Abstract BACKGROUND: Pai syndrome (PS) is a rare regional developmental defect of the face, mainly characterized by the variable association of midline cleft of the upper lip (MCL), duplicated maxillary median frenulum, and midline facial cutaneous and midanterior alveolar process polyps. Its entire clinical spectrum is still poorly delineated and the etiology remains unknown. CASE: We describe a 1-month-old boy presenting with MCL, left nostril hamartomatous mass, midline pedunculated polyp originating from the columella base, midline alveolar cleft, duplication of the upper median frenulum, unilateral persistent papillary membrane, lipoma of the corpus callosum, and additional minor facial dysmorphism. This patient also presents with agenesis of the corpus callosum, which has never been reported in PS. Literature review was carried out comparing clinical data of the 20 previously published patients with those observed in the present case. CONCLUSIONS: The minimum diagnostic criteria for PS has been fixed in one or more hamartomatous nasal polyps plus MCL (with or without cleft alveolus) and/or midanterior alveolar process congenital polyp. Additional common ancillary findings include duplicated median maxillary frenulum, hypertelorism, nasal cleft, midfrontal skin tags, and ocular and CNS structural abnormalities. However, mental retardation is only an occasional feature and seems to be related to coexisting conditions (such as chromosome imbalance). Literature review shows that PS is etiologically heterogeneous, as it may result from chromosome abnormalities and environmental/stochastic events, as well as de novo mutations. Birth Defects Research (Part A) 2007. © 2007 Wiley-Liss, Inc. [source] Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoidesBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2002X. Mao Summary Background Data on genome-wide surveys for chromosome aberrations in primary cutaneous T-cell lymphoma (CTCL) are limited. Objectives To investigate genetic aberrations in CTCL. Methods We analysed 18 cases of Sézary syndrome (SS) and 16 cases of mycosis fungoides (MF) by comparative genomic hybridization (CGH) analysis, and correlated findings with the results of additional conventional cytogenetics, fluorescent in situ hybridization (FISH) and allelotyping studies. Results CGH analysis showed chromosome imbalances (CIs) in 19 of 34 CTCL cases (56%). The mean ±,SD number of CIs per sample was 1·8 ± 2·4, with losses (1·2 ± 2·0) slightly more frequent than gains (0·6 ± 1·0). The most frequent losses involved chromosomes 1p (38%), 17p (21%), 10q/10 (15%) and 19 (15%), with minimal regions of deletion at 1p31p36 and 10q26. The commonly detected chromosomal gains involved 4/4q (18%), 18 (15%) and 17q/17 (12%). Both SS and late stages of MF showed a similar pattern of CIs, but no chromosomal changes were found in three patients with T1 stage MF. Of the 18 SS cases also analysed by cytogenetics, seven showed clonal chromosome abnormalities (39%). Five cases had structural aberrations affecting chromosomes 10 and 17, four demonstrated rearrangement of 1p and three revealed an abnormality of either 6q or 14q consistent with CGH findings. FISH analysis showed chromosome 1p and 17q rearrangements in five of 15 SS cases, and chromosome 10 abnormalities in four SS cases consistent with both the G-banded karyotype and the CGH results. In addition, allelotyping analysis of 33 MF patients using chromosome 1 markers suggested minimal regions of deletion at D1S228 (1p36), D1S2766 (1p22) and D1S397 (1q25). Conclusions These findings provide a comprehensive assessment of genetic abnormalities in CTCL and a rational approach for further studies. [source] Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11)GENES, CHROMOSOMES AND CANCER, Issue 4 2003Toshihiko Imamura In this study, we examined a pediatric case of therapy-related myelodysplastic syndrome (tMDS). The symptoms developed 17 months after treatment for acute myeloblastic leukemia (AML, M2 subtype according to the French,American,British [FAB] classification) involving a chromosome abnormality at t(8;21)(q22;q22). Upon diagnosis of tMDS, spectral karyotyping analysis detected a new chromosomal translocation at t(2;8)(p23;p11.2). In addition, fluorescence in situ hybridization analysis suggested a rearrangement in the monocytic leukemia zinc finger (MOZ) gene, located in the 8p11 region of chromosome 8. However, no partner gene on 2p23 could be identified. To our knowledge, this is the first report of tMDS associated with a rearrangement of the MOZ gene. MOZ-linked fusion proteins such as MOZ-CBP (CREB binding protein), MOZ-TIF2 (transcriptional intermediary factor 2), and MOZ-p300 (adenoviral E1A-associated protein) are associated with AML chromosomal abnormalities at t(8;16)(p11;p13), inv(8)(p11q13), and t(8;22)(p11;q13), respectively, and are thought to account for leukemogenesis occurring through the aberrant regulation of histone acetylation. Through a similar mechanism, we believe that MOZ, fused to an unidentified partner gene at 2p23, may have caused an alteration in histone acetylation, resulting in the development of tMDS in this patient. © 2003 Wiley-Liss, Inc. [source] In vitro Epstein-Barr virus-immortalized lymphoma cell line carrying t(9;14)(p13;q32) chromosome abnormality, derived from splenic lymphoma with villous lymphocytesINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Masanori Daibata Abstract We herein describe splenic lymphoma with villous lymphocytes (SLVL) carrying t(9;14)(p13;q32). The t(9;14)(p13;q32) is a rare reciprocal chromosome translocation found in a subset of B-cell malignancies, mainly in low-grade non-Hodgkin's lymphomas. In t(9;14)(p13;q32), PAX-5 gene on 9p13 is involved with the immunoglobulin heavy-chain gene on 14q32. It has been thought that the deregulated expression of PAX-5 as a result of t(9;14)(p13;q32) may contribute to abnormal cell proliferation. Although continuous cell lines are invaluable tools for studying lymphomagenesis in the t(9;14)(p13;q32)-bearing lymphomas, establishment of such cell lines is extremely difficult since they are usually mature B-cell malignancies. In an attempt to transform the SLVL cells into a proliferating cell line, we examined the responses of the cells to infection by Epstein-Barr virus (EBV). SLVL cells were found to be susceptible to immortalization by EBV, resulting in a permanent cell line. The cell line, designated SL-15, possessed the t(9;14)(p13;q32). Genotype analysis and immunophenotype profiles confirmed that the cell line arose from the primary lymphoma cells. The cells had characteristic cytoplasmic villi. SL-15 cells has been growing over 2 years equivalent to 350,400 population doubling levels without proliferative crisis that is often observed in EBV-positive lymphoblastoid cell lines. Furthermore, SL-15 cells, when inoculated into nude mice, formed t(9;14)(p13;q32)-bearing tumors with cytoplasmic villi. The validated SLVL-derived cell line provide a useful model system to study molecular biology of t(9;14)(p13;q32)-bearing B-cell malignancies as well as lymphomagenesis of SLVL in vitro and in vivo. © 2005 Wiley-Liss, Inc. [source] Erythropoietin-resistant anaemia in a predialysis patient with Klinefelter syndromeNEPHROLOGY, Issue 2 2005Case Report SUMMARY: A diabetic predialysis patient who had significantly reduced sensitivity to erythropoietin therapy was admitted to Tsukuba University Hospital. Many factors that might have been the cause of the erythropoietin resistance were examined, and a diagnosis of refractory anaemia was made based on a bone marrow aspiration biopsy. A cytogenetic abnormality (47, XXY) was also detected in the bone marrow biopsy specimen, and hence the patient was also diagnosed with Klinefelter syndrome. It was suspected that the sex chromosome abnormality influenced glucose intolerance, renal insufficiency, and erythropoietin resistance due to myelodysplastic changes in the bone marrow. [source] Comparison of microarray-based detection rates for cytogenetic abnormalities in prenatal and neonatal specimensPRENATAL DIAGNOSIS, Issue 9 2008Lisa G. Shaffer Abstract Objective To compare the detection rate by microarray analysis for chromosome abnormalities in a prenatal population to that of a neonatal population referred for diagnostic testing. Methods Array comparative genomic hybridization (aCGH) analysis was performed for 151 prenatal cases and compared with the results from 1375 postnatal cases less than 3 months of age. Results Two of 151 prenatal cases (1.3%) showed a clinically significant cytogenetic abnormality. In contrast, of the 1375 postnatal cases studied, 11.4% showed a cytogenetic abnormality by aCGH. Many of these (40%) were referred for aCGH because of dysmorphic features, a clinical indication unlikely to be identified in the prenatal population. Conclusions The chance of detecting a chromosome abnormality in a prenatal population that has already been screened by routine cytogenetics is ,1.3%. However, given that many of the abnormal array results in the neonatal population were among those with dysmorphic features as the primary indication for testing, which are not easily identifiable by ultrasound, offering prenatal testing by aCGH to a wider population would likely result in a higher detection rate. Copyright © 2008 John Wiley & Sons, Ltd. [source] Pregnancy outcome in the setting of extremely low first trimester PAPP-A levelsAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2009Fergus SCOTT Background: Serum pregnancy-associated plasma protein-A (PAPP-A) is part of first trimester Down syndrome screening. Low levels have been associated with adverse outcome as well as chromosomal abnormality. Aims: To assess the incidence of adverse outcome when PAPP-A levels are at or below 0.2 multiples of the median (MoM). Methods: Data on consecutive patients attending a first trimester screening program were collected. Those with PAPP-A levels , 0.2 MoM were divided into three groups: , 0.1 MoM; 0.11,0.15 MoM; and 0.16,0.2 MoM. Results: Screening 44 535 patients resulted in 197 with PAPP-A levels , 0.2 MoM. The incidence of karyotypic abnormality increased with decreasing PAPP-A levels. In the absence of chromosome abnormality, pregnancy outcomes were defined as ,normal' in at least 30% and ,good' in at least 60%, with both percentages increasing as the PAPP-A level rose. The PAPP-A levels were significantly lower in the group with a poor outcome. The incidence of prematurity was similar in the three groups, but higher than the statewide average, while the incidence of extreme prematurity appeared to be related to reducing PAPP-A levels. The incidence of growth restriction in the three groups was similar, but was still double the incidence in the normal population. Conclusion: If the PAPP-A level is , 0.2 MoM and the karyotype is normal, there is an increased risk of adverse outcome. Even with PAPP-A below 0.1 MoM, a good outcome can be expected in 60% of cases. Careful morphological assessment is suggested and later monitoring of fetal growth and well-being. [source] | |||||||||||||