Partial Trisomy Of Chromosome Research Articles

Divergent leukaemia subclones as cellular models for testing vulnerabilities associated with gains in chromosomes 7, 8 or 18

Haematopoietic malignancies are frequently characterized by karyotypic abnormalities. The development of targeted drugs has been pioneered with compounds against gene products of fusion genes caused by chromosomal translocations. While polysomies are equally frequent as translocations, for many of them we are lacking therapeutic approaches aimed at synthetic lethality. Here, we report two new cell lines, named MBU-7 and MBU-8, that differ in complete trisomy of chromosome18, a partial trisomy of chromosome 7 and a tetrasomy of the p-arm of chromosome 8, but otherwise share the same mutational pattern and complex karyotype. Both cell lines are divergent clones of U-937 cells and have the morphology and immunoprofile of monocytic cells. The distinct karyotypic differences between MBU-7 and MBU-8 are associated with a difference in the specific response to nucleoside analogues. Taken together, we propose the MBU-7 and MBU-8 cell lines described here as suitable in vitro models for screening and testing vulnerabilities that are associated with the disease-relevant polysomies of chromosome 7, 8 and 18.

Report of a case with partial trisomy 9 mosaicism

Trisomy 9 syndrome and other related abnormalities such as full or mosaic trisomy 9 are very rare human chromosomal disorders. The disorders cause early pregnancy loss or death within 20 days after the birth which is accompanied by complex birth defects. The case reported here is a 26-year-old female, identified with partial trisomy of chromosome 9 by Array comparative genomic hybridization -aCGH, but has a longer life than reported in the medical literature and can give birth. The patient did not have abnormal mental or motor problems; no morphological ultrasound abnormalities; curved thumb and scattered warts on the left hand; gave birth to a healthy son after three consecutive stillbirths. The report has shown diverse clinical manifestations of trisomy 9 mosaic abnormalities in humans, contributing to a rare data source of trisomy 9 mosaic cases. Since then, improve knowledge of genetic counseling for rare cases of trisomy 9 mosaicism, especially in genetic counseling of prenatal diagnosis.

STRUCTURAL VARIATIONS OF CHROMOSOME 9

Partial trisomy of chromosome 9 has relatively frequently been observed in liveborn subjects. In the majority of the reported cases breaks occur in the centric segment of the long arm (q11-q13). Two characteristics of this chromosome part, i.e. 9qh+ and inv(9), have been studied. The results of a study of selected samples do not support an association between 9qh+ chromosome anomaly and reproductive failure. The frequency of inv(9) in different samples agrees with those reported by other investigators (1.11—2.32%). An excess of male carriers was found. Aneusomy of recombination has been observed in one case. Partial trisomy of chromosome seems to be the most frequently observed type of unbalanced structural aberration of autosomes in liveborn subjects. Up to now 50 cases have been reported. Three of these have been described as 9q trisomy, the others were 9p trisomies

Features of cytogenetic diagnosis of simultaneous chronic lymphocytic leukemia and myelodysplastic syndrome: clinical case report

In chronic lymphocytic leukemia, the risk of second tumors including hematological malignancies, with which the use of purine nucleosides and alkylating agents in treatment of chronic lymphocytic leukemia is most often associated, is significantly increased. Concurrent detection of this disease and various hematological tumors is a rare occurrence in hematological practice. Use of cytogenetic method or analysis allows to differentiate between 2 tumors and confirm differences in genetic abnormalities in different clones and on different levels of cell differentiation. This article presents a clinical case of simultaneous chronic lymphocytic leukemia and myelodysplastic syndrome with 2 clones with different cytogenetic abnormalities: partial trisomy of chromosome 12 and deletion of the long arm of chromosome 5 formed at different levels of cell differentiation.

46,XY,9(p24)dup(2q35q37.3) with Cryptorchidism: A Case Report and Literature Review

A young boy with a facial abnormality was brought to our genetics clinic. Physical examination found bilateral cryptorchidism. Several clinical genetic tests, including chromosome microarray analysis (CMA), karyotyping, and azoospermia factor (AZF) microdeletions on the Y chromosome, were used to identify the genetic basis for this abnormality. The karyotype showed a duplication of the chromosome 2q35q37.3 fragment attached to chromosome 9(p24); CMA revealed 2q35q37.3(220,558,895-243,006,013)x3; the Y chromosome showed no AZF microdeletions; and the parent karyotypes were normal. Surgery has been planned to correct cryptorchidism a year after the original examination. A similar case was found previously. Key words: Azoospermia Factor; Chromosome Microarray Analysis; Cryptorchidism; Karyotype; Partial Trisomy of Chromosome

A Child with Partial Trisomy 4 (q26 – qterminal) Resulting from Paternally Inherited Translocation (4:18) Associated with Multiple Congenital Anomalies and Death

Parental balanced reciprocal translocations can result in partial aneuploidy in the offspring due to unbalanced meiotic segregation during gametogenesis. Herein, we report the phenotypic and cytogenetic characterization in a 9-day-old male child with partial trisomy of chromosome 4. Karyotyping of the proband and parents was performed along with multicolor fluorescence in situ hybridization (mFISH) of paternal chromosomes. Conventional cytogenetic analysis by karyotyping showed 47,XY,der(18),t(4;18)(q26;q22),+4 in proband, and the paternal karyotype was found as 47,XY,der(18),t(4;18)(q26;q22). mFISH analysis on paternal chromosomal preparations confirmed both region and origin of the balanced translocation. In this study, karyotyping helped us to identify both numerical and structural anomalies in the proband, and mFISH helped us to confirm our cytogenetic findings. Therefore, cytogenetic screening of both partners is recommended before pregnancy to rule out or confirm the presence of any numerical or structural anomaly in one, both, or none of the partners.

Partial trisomy of chromosome 9 with congenital anomalies

Partial trisomy of chromosome 9 with congenital anomalies

Characterization of a balanced complex chromosomal rearrangement carrier ascertained through a fetus with dup15q26.3 and del5p15.33: case report

Complex chromosomal rearrangements (CCRs) are structural aberrations involving more than two chromosomes which rarely appear in individuals with normal phenotypes. These individuals report fertility problems, recurrent miscarriages, or congenital anomalies in newborn offspring as a consequence of either meiotic failure or imbalanced chromosome segregation. A CCR involving chromosomes 5, 15, and 18 was discovered in a phenotypically normal man through a fetus with congenital malformations and partial trisomy of chromosome 15 and monosomy of chromosome 5. Ultrasound examination at 20 weeks of gestation showed severe oligoamnios and hydrothorax. Prenatal cytogenetic analysis and array comparative genomic hybridization (array-CGH) revealed a female fetus with dup15q26.3 and del5p15.33. We diagnosed the CCR using three-color fluorescence in situ hybridization (three-color FISH), and a balanced CCR using array-CGH and FISH was diagnosed in the paternal karyotype. The father is a carrier of a balanced translocation 46,XY,t(5;15;18)(p15.31;q26.3;p11.2). Due to the complexity of these rearrangements the diagnosis is difficult and the reproductive outcome uncertain. Reporting such rare cases is important to enable such information to be used for genetic counseling in similar situations and help estimate the risk of miscarriage or of newborns with congenital abnormalities.

Distinctive neurological phenotype associated with partial trisomy of chromosome 16

We present a case of a live born female infant who presented in early life with a movement disorder, lack of developmental progress and neutropenia. Extensive neuro-metabolic investigation was non-diagnostic. Chromosome analysis of cultured lymphocyte cells showed an abnormal chromosome 16 with additional material noted in the proximal long arm. Additional fluorescence in situ hybridisation studies identified this additional material to represent a duplication of the long arm of chromosome 16 between 16q11.2 and 16q21. There was progressive decline and death by 10 months. Dystonia cortical blindness and neutropenia have not been a reported feature of trisomy 16 to date.

Diagnóstico prenatal de un caso de trisomía 8 mosaico, asociado a la existencia de un quiste unilateral de plexos coroideos

We report a case of trisomy 8 mosaicism, diagnosed by FISH (fluorescent in situ hibridization) after 18 week pregnancy amniocentesis, in a patient whose ultrasound scan showed a unilateral choroid plexus cyst and placental haemangioma.We assessed the foetopathological examination, comparing it with different cases of total and partial trisomies of chromosome 8, paying special attention to the relationship between choroid plexus cyst and chromosomopathies.

Is There a Yet Unreported Unbalanced Chromosomal Abnormality without Phenotypic Consequences in Proximal 4p?

Unbalanced chromosomal abnormalities (UBCA) are reported for >50 euchromatic regions of almost all human autosomes. UBCA are comprised of a few megabases of DNA, and carriers are in many cases clinically healthy. Here we report on a partial trisomy of chromosome 4 of the centromere-near region of the short arm of chromosome 4 present as a small supernumerary marker chromosome (sSMC). The sSMC was present in >70% of amnion cells and in 60% of placenta. Further delineation of the size of the duplicated region was done by molecular cytogenetics and array comparative genomic hybridization. Even though the sSMC lead to a partial trisomy of ∼9 megabase pairs, a healthy child was born, developing normally at 1 year of age. No comparable cases are available in the literature. Thus, we discuss here the possibility of having found a yet unrecognized chromosomal region subject to UBCA.

Chromosomal rearrangements and their role in spontaneous immortalization and transformation of rat embryo cells in vitro

G-banding analysis of LRec-1 and LRec-3, spontaneously immortalized cell lines from rat embryo fibroblast, revealed diploid karyotypes with specific clonal structural rearrangements of chromosomes 7 and 19 - del(7)(q11.2q22.1), t(7;19)(q11.1;q12) in malignant stage. Both clonal abnormalities of chromosomes 7 and 19 were also revealed in LRec-1k clone and LRec-1 sf cell line. Previous study of LRec-1 and LRec-3 cells showed the presence of karyotypes with pseudodiploid modal chromosome number, partial trisomy of chromosome 7 and same clonal structural rearrangements of chromosomes 7 and 19 in immortalized stage. In malignant stage, the trisomy 6 and new clonal structural rearrangements of chromosomes 1, 2, 11, 15, 18, 19 and of chromosomes 10, 20 were also found in LRec-1 sf and LRec-1 cells, accordingly. There were no new clonal structural chromosome rearrangements in LRec-1 k and LRec-3 cells. We compared locies of chromosomes involved in rearrangements with mapped genes on these chromosomes according to RATMAP. Supposedly these genes are involved in spontaneous immortalization of rat embryo fibroblast and malignant transformation of LRec-1 and LRec-3 cells and rearrangements of chromosomes 1, 2, 11, 15 and 18 facilitate expression of growth factors of LRec-1 sf cells.

Rearrangements of MALT1, IgH, FOXP1, BCL3 and PAX5 Are Rare Events in Extranodal Marginal Zone Lymphoma in the UK.

A number of balanced translocations have been described in extranodal marginal zone lymphoma (ENMZL). The t(11;18) and variant t(14;18) which deregulate MALT1 are the commonest reported occurring in up to 40% of patients. The t(3;14) which deregulates FOXP1 is reported to occur in up to 10% of cases whilst the t(1;14) and t(14;19) which deregulate BCL10 and BCL3 respectively have been described in a variable proportion of patients. The purpose of this study was to evaluate the incidence of such abnormalities in the routine diagnostic setting in a geographically defined region of Northern England. We have therefore reviewed a series of 56 consecutive cases of presenting ENMZL, diagnosed between November 2003 and July 2006 in the Yorkshire and Humberside Haematology Network (YHHN), which serves a population of approximately 3.6 million. Diagnoses were made using WHO criteria. Presentation tissue included breast (2), gastric (29), colon (3), Conjuctiva/orbit (3), connective tissue/muscle (3), lung (2), parotid (2), salivary gland (2), thyroid (1), prostate (2), and skin (4). In 2 cases the site was unknown. All cases were investigated for MALT1 rearrangements with an alpha satellite 18 control (VYSIS 32-190055/D18Z1) using interphase FISH at the time of diagnosis. Cases with available biopsy material were further investigated for rearrangements of IgH, (VYSIS 32-191019), PAX5, BCL3 (DAKO Y5413 and Y5411) and FOXP1 (in-house probe). FISH was perormed on thin paraffin sections in 54/56 cases and on fresh tissue imprints in 2 cases. 6/56 (11%) cases demonstrated a rearrangement of MALT1, 5/6 were of gastric origin and 1 colonic. 16/56 (29%) cases demonstrated trisomy 18. 6/44 (14%) cases showed rearrangement of IgH (3/6 were unbalanced rearrangement with loss). In 1 of these cases (gastric) BCL3 was also rearranged, suggesting that this may represent a t(14;19)(q32;q13). 1 additional case (parotid) showed an unbalanced rearrangement of BCL3 with loss of the telomeric portion of the gene, giving a total of 2/30 (7%) cases with BCL3 abberrations. In the latter case no other abnormalities were demonstrated. A further 5 cases were suspicious for IgH rearrangements with a low level of cells (<10%) showing rearrangement. No cases were demonstrated to have rearrangement of PAX5 or FOXP1, but 6/32 (19%) cases showed 3 copies of PAX5 and similarly 7/30 (23%) had extra copies of FOXP1, consistent with complete or partial trisomy of chromosomes 9 and 3.The incidence of MALT1 rearrangements in this study is significicantly lower than most published series. The reasons for this apparrent discrepancy is unclear at present but this study represents a consecutive series of patients presenting in a defined UK cancer network and is therefore free from any referral bias. We similarly failed to demonstrate rearrangements of either FOXp1 or PAX5. Rearrangement of BCL3 was however demonstrated but at low frequency. It is clear that although significant advances have been made in our understanding of the pathobiology of ENMZL the underlying cytogenetic defect remains unknown in the majority of patients.

Cleft palate associated with an unbalanced karyotype in piglets sired by a heterozygous carrier boar with a balanced constitutional reciprocal translocation

The progeny of a commercial (Landrace x Duroc) x Large White boar contained a number of piglets with cleft palates. Chromosomal analyses of five affected piglets showed that they all...

Two unbalanced segregation products due to a maternal t(7;16)inv(16)

We report a prenatal case of a maternally inherited abnormal chromosome 16, originally interpreted as a pericentric inversion only, but after family studies re-interpreted as a pericentric inversion (16) accompanied by an unbalanced (7;16) translocation. Because of the inversion 16 and an elder son with developmental delay and craniofacial dysmorphic features, in the past karyotyped as 46,XY, the chromosomes 16 of the mother and son were carefully re-examined. Using a whole chromosome 16 paint and sub-telomere probes of 16p and 16q, the karyotype of the mother was shown to be 46,XX,inv(16)(p11.2q23.2).ish t(7;16)(q36;p13.3)inv(16). Subsequently one chromosome 16 of the elder son appeared to be a der(16)t(7;16)(q36;p13.3). This is probably the result of a meiotic crossover between the chromosomes 16 in the mother. The prenatal karyotype was finally interpreted as 46,XY,inv(16)(p11.2q23.2).ish der(16)t(7;16)(q36;p13.3)inv(16). This is the same cytogenetic imbalance as his elder brother: a partial trisomy of chromosome 7 (q36-->qter) and a partial monosomy of chromosome 16 (p13.3-->pter).

Anterior segment dysgenesis and congenital glaucoma associated with partial trisomy of chromosome 1 (1q32-qter)

A child born with partial trisomy of chromosome 1 (1q32-qter) survived and was seen for anterior segment dysgenesis and congenital glaucoma. Pure trisomy 1q is rarely seen in live-born infants and has not previously been described in association with congenital glaucoma. The genetic basis for glaucoma is complicated and multifactorial and probably determined by a number of genes on a variety of chromosomes. The current case provides some evidence that part of chromosome 1 may be involved with the etiology of a glaucomatous process.

Preimplantation genetic diagnosis of chromosome balance in embryos from a patient with a balanced reciprocal translocation.

Duplications or deletions are present in a high percentage of the gametes produced by individuals carrying balanced translocations. Preimplantation genetic diagnosis was used to examine chromosome balance in embryos from a patient having a reciprocal translocation within the short arms of chromosomes 5 and 8 (46,XX,t(5;8)(p13;p23)). This woman has two sisters with the translocation unbalanced, resulting in a partial trisomy for chromosome 5 and partial monosomy for chromosome 8 (46,XX,-8, +der(8)t(5;8)(p13;p23)) with associated mental retardation and physical abnormalities. The patient and her husband desired to have children without the abnormal chromosome balance and wished to reduce the likelihood of spontaneous abortion or need for therapeutic abortion. Fluorescence in-situ hybridization (FISH) probes for the alpha-satellite region of chromosome 8 and for a region on the short arm of chromosome 5 (5p15.2) were tested initially on lymphocytes from the patient and her sisters. The hybridization signal for chromosome 5 was detected in the expected two copies for the patient and three copies for the sisters in 87% of the cells. Two hybridization signals for chromosome 8 were detected in 96% of the cells from all individuals. Additional probe testing was done using blastomeres from polyspermic embryos. The couple then proceeded with a stimulated in-vitro fertilization (IVF) cycle and biopsies were done on 13 embryos at the 7-10-cell stage using a method of zona drilling and fluid displacement. Diagnosis was possible on at least one blastomere for nine embryos. Three embryos had nuclei with three hybridization signals for chromosome 5, three had fewer than two signals for one or both chromosomes, one was mosaic, and two had two signals for each chromosome. The latter were transferred to the patient, but pregnancy was not achieved. The results demonstrate that preimplantation genetic diagnosis for patients with reciprocal translocations can be used to identify embryos having normal chromosome balance. The potential advantages and limitations of this approach are discussed.

PRENATAL DIAGNOSIS OF A HALF-CRYPTIC TRANSLOCATION USING CHROMOSOME MICRODISSECTION

This report describes a case of a paternal balanced, but apparently non-reciprocal, insertion of chromosome 15 material into the short arm of chromosome 17 with difficulties in distinguishing between the normal and the deleted chromosome 15 in prenatal karyotype analysis. Microdissection and degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) of the paternal 17p+ chromosome was performed to generate a painting probe specific for the small region inserted from chromosome 15 into chromosome 17. Fluorescence in situ hybridization (FISH) of this probe simultaneously with a differentially labelled 15q microdissection probe enabled the identification of a balanced karyotype in the fetus. In this case, microdissection combined with FISH was the only method for obtaining a reliable result within the short time available for prenatal diagnosis. In addition, it was possible to identify with certainty the originally suspected reciprocal translocation as an insertion of the region 15q22.3-->q23 or 24 into the sub-telomeric region of 17p [ins(17;15)(p13;q22.3q23 or 24)]. Thus, the chromosomal defect of two family members with a partial trisomy of chromosome 15 having severe mental retardation and dysmorphic features was identified precisely.

Valproate-Induced Lupus Erythematosus

A mentally retarded 30-year-old woman with partial trisomy of chromosome 9, suffering from epilepsy since age 11 months, developed systemic lupus erythematosus after one year of treatment with valproate (VPA) and ethosuximide (ESM) at the Clinica Neurologica, Universita di Roma Tor Vergata, Italy.

Psychiatric disorder in a familial 15;18 translocation and sublocalization of myelin basic protein to 18q22.3

Two related patients with similar clinical features consisting of a few dysmorphic signs and psychiatric disturbance were reported to have a partial trisomy of chromosomes 15(pter-q13.3) and 18(q23-qter) deriving from a familial translocation t(15;18). One patient is affected by bipolar disorder and the other by schizoaffective disorder. Both cases have a predominantly affective course; nevertheless, a clear diagnosis is difficult in the first patient, who is 15 years of age, and only a longitudinal course will allow us to establish a definite diagnosis. The possibility that these two pathologies belong to a single category is discussed, and the presence of a susceptibility locus on chromosome 18 is hypothesized. Cytogenetic data, FISH, and DNA studies indicate that the myelin basic protein (MPB) gene is not involved in the translocation, and localize it centromeric to the breakpoint on chromosome 18(q22.3). Thus, it is unlikely to be involved in the disease.