Unexpected Coexistence of a Derivative t(21;21) and Complementary Mosaic r(21) in a Female with Multiple Miscarriages

2019 ◽  
Vol 158 (2) ◽  
pp. 83-87
Author(s):  
Duygu Onur Cura ◽  
Elcin Bora ◽  
Hande Ozkalayci ◽  
Ozgur Kirbiyik ◽  
Yasar B. Kutbay ◽  
...  
Keyword(s):  
Female Patient ◽  
Microarray Analysis ◽  
Trisomy 21 ◽  
Ring Chromosome ◽  
Partial Trisomy ◽  
Chromosome 21 ◽  
Fish Analysis ◽  
Recurrent Miscarriages ◽  
Conventional Cytogenetics ◽  
Diagnostic Importance

The case presented here describes a female patient with recurrent miscarriages and a normal microarray analysis result. However, the coexistence of a robertsonian (21;21) translocation and complementary mosaic ring chromosome 21 was detected by karyotyping and FISH analysis. Partial trisomy 21 was found with QF-PCR and microarray analysis in one of the fetuses. The aim of this report was to emphasize the diagnostic importance of conventional cytogenetics.

scholarly journals Partial trisomy 21 map: Ten cases further supporting the highly restricted Down syndrome critical region (HR‐DSCR) on human chromosome 21

2019 ◽  
Vol 7 (8) ◽  
Author(s):  
Maria Chiara Pelleri ◽  
Elena Cicchini ◽  
Michael B. Petersen ◽  
Lisbeth Tranebjærg ◽  
Teresa Mattina ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Human Chromosome ◽  
Critical Region ◽  
Trisomy 21 ◽  
Partial Trisomy ◽  
Chromosome 21 ◽  
Human Chromosome 21

scholarly journals A de novo 2.78-Mb duplication on chromosome 21q22.11 implicates candidate genes in the partial trisomy 21 phenotype

2016 ◽  
Vol 1 (1) ◽  
Author(s):  
James D Weisfeld-Adams ◽  
Amanda K Tkachuk ◽  
Kenneth N Maclean ◽  
Naomi L Meeks ◽  
Stuart A Scott
Keyword(s):  
Candidate Genes ◽  
Clinical Features ◽  
Critical Region ◽  
Trisomy 21 ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Partial Trisomy ◽  
Chromosome 21 ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic

Abstract Down syndrome (DS) is the most common genetic cause of intellectual disability (ID) and in the majority of cases is the result of complete trisomy 21. The hypothesis that the characteristic DS clinical features are due to a single DS critical region (DSCR) at distal chromosome 21q has been refuted by recently reported segmental trisomy 21 cases characterised by microarray-based comparative genomic hybridisation (aCGH). These rare cases have implicated multiple regions on chromosome 21 in the aetiology of distinct features of DS; however, the map of chromosome 21 copy-number aberrations and their associated phenotypes remains incompletely defined. We report a child with ID who was deemed very high risk for DS on antenatal screening (1 in 13) and has partial, but distinct, dysmorphologic features of DS without congenital heart disease (CHD). Oligonucleotide aCGH testing of the proband detected a previously unreported de novo 2.78-Mb duplication on chromosome 21q22.11 that includes 16 genes; however, this aberration does not harbour any of the historical DSCR genes (APP, DSCR1, DYRK1A and DSCAM). This informative case implicates previously under-recognised candidate genes (SOD1, SYNJ1 and ITSN1) in the pathogenesis of specific DS clinical features and supports a critical region for CHD located more distal on chromosome 21q. In addition, this unique case illustrates how the increasing resolution of microarray and high-throughput sequencing technologies can continue to reveal new biology and enhance understanding of widely studied genetic diseases that were originally described over 50 years ago.

scholarly journals Monosomy 21 Seen in Live Born Is Unlikely to Represent True Monosomy 21: A Case Report and Review of the Literature

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Trent Burgess ◽  
Lilian Downie ◽  
Mark D. Pertile ◽  
David Francis ◽  
Melissa Glass ◽  
...  
Keyword(s):  
Chromosome Region ◽  
Ring Chromosome ◽  
Chromosome Analysis ◽  
Peripheral Blood Lymphocytes ◽  
Terminal Segment ◽  
Chromosome 21 ◽  
Molecular Testing ◽  
Fish Analysis ◽  
Nasal Bridge ◽  
Monosomy 21

We report a case of a neonate who was shown with routine chromosome analysis on peripheral blood lymphocytes to have full monosomy 21. Further investigation on fibroblast cells using conventional chromosome and FISH analysis revealed two additional mosaic cell lines; one is containing a ring chromosome 21 and the other a double ring chromosome 21. In addition, chromosome microarray analysis (CMA) on fibroblasts showed a mosaic duplication of chromosome region 21q11.2q22.13 with approximately 45% of cells showing three copies of the proximal long arm segment, consistent with the presence of a mosaic ring chromosome 21 with ring instability. The CMA also showed complete monosomy for an 8.8 Mb terminal segment (21q22.13q22.3). Whilst this patient had a provisional clinical diagnosis of trisomy 21, the patient also had phenotypic features consistent with monosomy 21, such as prominent epicanthic folds, broad nasal bridge, anteverted nares, simple ears, and bilateral overlapping fifth fingers, features which can also be present in individuals with Down syndrome. The patient died at 4.5 months of age. This case highlights the need for additional studies using multiple tissue types and molecular testing methodologies in patients provisionally diagnosed with monosomy 21, in particular if detected in the neonatal period.

scholarly journals Diagnosis of Trisomy 21 in Fetal Nucleated Erythrocytes from Maternal Blood by Use of Short Tandem Repeat Sequences

2001 ◽  
Vol 47 (9) ◽  
pp. 1622-1626 ◽  
Author(s):  
Osamu Samura ◽  
Satoshi Sohda ◽  
Kirby L Johnson ◽  
Barbara Pertl ◽  
Steven Ralston ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Trisomy 21 ◽  
Pcr Amplification ◽  
Maternal Blood ◽  
Chromosome 21 ◽  
Fish Analysis ◽  
Str Markers ◽  
Fetal Aneuploidy ◽  
Fluorescent Pcr ◽  
Short Tandem

Abstract Background: The purpose of this study was to determine whether aneuploid fetal nucleated erythrocytes (NRBCs) could be detected in maternal blood through the use of fluorescent PCR amplification with polymorphic short tandem repeat (STR) markers as an alternative or complementary method to analysis by fluorescent in situ hybridization (FISH). Methods: Peripheral blood samples were obtained from women who had just undergone termination of pregnancy because of fetal trisomy 21 (three cases, 47,XY,+21; four cases, 47,XX,+21). Candidate fetal cells were isolated by flow-sorting by antibodies to the γ chain of fetal hemoglobin and Hoechst 33342. FISH analysis was performed by the use of chromosome-specific probes for X, Y, and 21. Fetal NRBCs, as defined by the presence of γ staining, characteristic morphology, and three chromosome 21 signals, along with maternal leukocytes, defined as γ negative and two chromosome 21 signals, were micromanipulated separately and subjected to fluorescent PCR amplification of chromosome 21 STR markers (D21S11, D21S1411, and/or D21S1412). Results: In five of seven cases analyzed, fetal NRBCs were aneuploid, as determined by the presence of triallelic or diallelic peaks of chromosome 21 sequences when compared with sequences from the maternal leukocytes. Conclusions: Fluorescent PCR amplification of STRs can detect fetal aneuploidy and may be useful in the setting of poor hybridization efficiency with FISH analysis. These results suggest that combined fetal aneuploidy and single-gene diagnoses by the use of DNA microarrays may be feasible in the near future.

Exploring the Pathogenesis of Down Syndrome-Related Myeloproliferative Disorders Using iPSCs

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 868-868
Author(s):  
Nishinaka Yoko ◽  
Akira Niwa ◽  
Mitsujiro Osawa ◽  
Akira Watanabe ◽  
Tatsutoshi Nakahata ◽  
...  
Keyword(s):  
Down Syndrome ◽  
B Lymphocytes ◽  
Trisomy 21 ◽  
Morphological Difference ◽  
Chromosome 21 ◽  
Fish Analysis ◽  
Transcription Activator ◽  
Differentiation Potential ◽  
Exon 2 ◽  
Gata1 Mutation

Abstract Down syndrome (DS) is a congenital syndrome due to the trisomy of chromosome 21. Transient myeloproliferative disorder (TMD) is its hematopoietic complication, affecting approximately 10% of DS-neonates. TMD is characterized by transient abnormal proliferation of blastic cells, and importantly, all TMD blasts bear mutations in GATA1 gene. Although TMD usually resolves spontaneously within 3 months after birth, twenty to thirty percent of TMD patients develop acute megakaryoblastic leukemia (AMKL) within several years afterward. This leukemogenic transition is considered as a good model for multi-step tumorigenesis. According to this putative multi-step model, the first hit should be additional chromosome 21, the second one is mutations on GATA1 gene which is requisite to the onset of TMD, and the “unknown” third hits are required for the progression into AMKL. However, it is still unclear that 1) how GATA1 mutation promotes TMD development, 2) what kinds of third hit are required for the onset of AMKL, and 3) why GATA1-mutated progenitors prevails during embryonic hematopoiesis only in trisomy 21 patients? In order to address these issues, a strictly controlled isogenic cell panels that can reproduce human emboryonic hematopoietic development is needed. Human induced pluripotent stem cells (iPSCs) derived from DS patients are a promising platform for this, but so far there is no report regarding GATA1-mutated TMD-associated iPSCs. Therefore, we set out to establish an iPSC panel that covers each genomic status of chromosome 21 and GATA1 gene. For this, we established both GATA1 mutant and wildtype clones from both trisomy 21 and disomy 21 clones. And we also established TMD patient derived iPSCs. First, we established isogenic iPSCs derived from EB virus immortalized B-lymphocytes of 2 mosaic DS patients. Frequency of trisomy 21 cells evaluated by FISH analysis and G-banding were 93% and 94% for each patient. We reprogrammed these cells by introducing 5 episomal vectors, pCE-hOCT3/4, pCE-hSK, pCE-hUL, pCE-mp53DD and pCXB-EBNA1, under feeder free condition. We genotyped each iPSC clones by digital-PCR analysis and found that the frequency of trisomy iPSC clones were comparable to that of trisomy cells in original EBV immortalized B-lymphocytes. There is no morphological difference between disomy and trisomy iPSC clones in both patients. We next introduced disease-associated GATA1 mutation into established isogenic trisomy and disomy iPS clones using transcription activator-like effector nuclease (TALEN) technology. We introduced a frameshift mutation in exon 2, which causes premature termination of the full-length transcript originated from 1st ATG and exclusively produces the shorter isoform of GATA1 (GATA1s) transcribed from 2nd ATG. Next, we obtained peripheral blood mononuclear cells (PBMCs) from a TMD patient in order to establish TMD-blast-derived iPSCs. Eighty-nine percent of nuclear cells in the PBMC fraction was CD117+CD45+ blastic cells, whereas only 5.6% were non-blast cells including CD3 positive T-lymphocytes, CD11b positive myeloid lineage cells and CD19 positive B-lymphocytes. The CD117+ cells showed TMD/AMKL blast-like appearance such as coarse choromatin pattern with nucleolus and bleb-like structures. We sorted out CD45+CD117+ blastic cells and CD45+CD117- non-blastic cells and successfully established iPSC clones from both populations. In conclusion, we successfully established a comprehensive panel of iPSC clones for evaluating the hematopoietic consequence associated with the GATA1 genotype and the ploidy of chromosome 21. We are currently evaluating hematopoietic differentiation potential of each clone and exploring the underlying pathophysiology of TMD/AMKL by using this platform. We believe that comprehensive understanding of TMD and AMKL pathogenesis provides a fruitful insight into our understanding of human leukemogenesis. Disclosures No relevant conflicts of interest to declare.

Cytogenetic, Molecular and FISH Analysis of an Isodicentric Chromosome 21 idic(21)(q22.3) in a Mildly-Affected Patient with Down Syndrome

2007 ◽  
Vol 7 (3) ◽  
pp. 215-218 ◽  
Author(s):  
Frenny J Sheth ◽  
Uppala Radhakrishna ◽  
Michael A Morris ◽  
Jean-Louis Blouin ◽  
Jayesh J Sheth ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Chromosome 21 ◽  
Fish Analysis ◽  
Affected Patient ◽  
Isodicentric Chromosome

RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3735-3741 ◽  
Author(s):  
Catherine Roche-Lestienne ◽  
Lauréline Deluche ◽  
Sélim Corm ◽  
Isabelle Tigaud ◽  
Sami Joha ◽  
...  
Keyword(s):  
Dna Binding ◽  
High Frequency ◽  
Trisomy 21 ◽  
De Novo ◽  
Blast Crisis ◽  
Clonal Evolution ◽  
Chronic Phase ◽  
Chromosome 21 ◽  
Imatinib Resistance ◽  
Molecular Abnormalities

Abstract Acquired molecular abnormalities (mutations or chromosomal translocations) of the RUNX1 transcription factor gene are frequent in acute myeloblastic leukemias (AMLs) and in therapy-related myelodysplastic syndromes, but rarely in acute lymphoblastic leukemias (ALLs) and chronic myelogenous leukemias (CMLs). Among 18 BCR-ABL+ leukemias presenting acquired trisomy of chromosome 21, we report a high frequency (33%) of recurrent point mutations (4 in myeloid blast crisis [BC] CML and one in chronic phase CML) within the DNA-binding region of RUNX1. We did not found any mutation in de novo BCR-ABL+ ALLs or lymphoid BC CML. Emergence of the RUNX1 mutations was detected at diagnosis or before the acquisition of trisomy 21 during disease progression. In addition, we also report a high frequency of cryptic chromosomal RUNX1 translocation to a novel recently described gene partner, PRDM16 on chromosome 1p36, for 3 (21.4%) of 14 investigated patients: 2 myeloid BC CMLs and, for the first time, 1 therapy-related BCR-ABL+ ALL. Two patients presented both RUNX1 mutations and RUNX1-PRDM16 fusion. These events are associated with a short survival and support the concept of a cooperative effect of BCR-ABL with molecular RUNX1 abnormalities on the differentiation arrest phenotype observed during progression of CML and in BCR-ABL+ ALL.

Trisomy 21 and isodicentric chromosome 21 in Kostmann syndrome following treatment with G-CSF

2001 ◽  
Vol 126 (1) ◽  
pp. 78-80 ◽  
Author(s):  
Birgitte Roland ◽  
Richard C Woodman ◽  
Keith Jorgenson ◽  
Alfredo Pinto
Keyword(s):  
Trisomy 21 ◽  
Chromosome 21 ◽  
Kostmann Syndrome ◽  
Isodicentric Chromosome

Molecular Cytogenetic Classification of Down Syndrome and Screening of Somatic Aneuploidy in Mothers

2021 ◽  
pp. 1-9
Author(s):  
Sushil Kumar Jaiswal ◽  
Ashok Kumar ◽  
Amit Kumar Rai
Keyword(s):  
Down Syndrome ◽  
Peripheral Blood ◽  
Trisomy 21 ◽  
Health Management ◽  
Chromosome 21 ◽  
Robertsonian Translocations ◽  
Significant Difference ◽  
And Control

Down Syndrome (DS) caused by trisomy 21 results in various congenital and developmental complications in children. It is crucial to cytogenetically diagnose the DS cases early for their proper health management and to reduce the risk of further DS childbirths in mothers. In this study, we performed a cytogenetic analysis of 436 suspected DS cases using karyotyping and fluorescent in situ hybridization. We detected free trisomies (95.3%), robertsonian translocations (2.4%), isochromosomes (0.6%), and mosaics (1.2%). We observed a slightly higher incidence of DS childbirth in younger mothers compared to mothers with advanced age. We compared the somatic aneuploidy in peripheral blood of mothers having DS children (MDS) and control mothers (CM) to identify biomarkers for predicting the risk for DS childbirths. No significant difference was observed. After induced demethylation in peripheral blood cells, we did not observe a significant difference in the frequency of aneuploidy between MDS and CM. In conclusion, free trisomy 21 is the most common type of chromosomal abnormality in DS. A small number of DS cases have translocations and mosaicism of chromosome 21. Additionally, somatic aneuploidy in the peripheral blood from the mother is not an effective marker to predict DS childbirths.

scholarly journals Distal Partial Trisomy 15q26 and Partial Monosomy 16p13.3 in a 36-Year-Old Male with Clinical Features of Both Chromosomal Abnormalities

2015 ◽  
Vol 145 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Devin M. Cox ◽  
Merlin G. Butler
Keyword(s):  
Intellectual Disability ◽  
Chromosomal Abnormalities ◽  
Receptor Gene ◽  
Partial Trisomy ◽  
Chromosome Translocation ◽  
Fish Analysis ◽  
Partial Monosomy ◽  
Chronic Anemia ◽  
Dysmorphic Features ◽  
History Of

We report a 36-year-old Caucasian male identified with distal partial trisomy 15q and partial monosomy 16p from an unbalanced chromosome translocation detected by microarray and FISH analysis. He had a history of developmental delay and intellectual disability, chronic anemia, tall and slender stature, thoracic scoliosis and lumbar lordosis, and dysmorphic features. The distal partial trisomy 15q included the insulin-like growth factor 1 receptor gene involved with growth, while genes in the distal partial monosomy 16p region are involved with alpha hemoglobin production, intellectual disability, dysmorphic features, and acromegaly. The chromosome derivative found in our patient contains genes known to play a role in his phenotype.

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