scholarly journals CHROMOSOMAL DISEASES IN THE HUMAN PATHOLOGY

2020 ◽  
Vol 6 (1) ◽  
pp. 50-60
Author(s):  
T.V. Bihunyak ◽  
Yu. I. Bondarenko ◽  
O. O. Кulyanda ◽  
S. M. Charnosh ◽  
A. S. Sverstiuk ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Dna Analysis ◽  
Klinefelter Syndrome ◽  
Basic Research ◽  
Multiple Birth ◽  
X Chromosomes ◽  
Screening Programs ◽  
Human Pathology ◽  
Chromosomal Diseases

Background. Chromosomal diseases are the cause of 45-50 % of multiple birth defects. Basic research on mutations is performed using genomic technologies to identify a correlation between genotype and phenotype in aneuploidies and to understand its pathogenesis. Objective. The aim of the research is to study the etiology, pathogenesis of symptoms and diagnostics for patients with Down, Klinefelter, Turner syndromes and double aneuploidies by 21 and sex chromosomes. Methods. A literature review by the keywords “Down syndrome”, “Klinefelter syndrome”, “Turner syndrome”, “double aneuploidy” for the period of 2000-2020 was carried out. Results. Down, Klinefelter and Turner syndromes are the most common aneuploidy among viable newborns. Frequency of meiotic non-disjunction events causing these aneuploidies increases with the age of a woman. Identified genes are responsible for pathogenesis of symptoms in trisomy 21, Turner and Klinefelter syndromes. Diagnostics of chromosomal diseases includes prenatal screening programs and postnatal testing. Conclusions. Cytogenetic variants of Down syndrome are simple complete trisomy 21, translocation form and mosaicism. Trisomy 21 is associated with advanced maternal age. Phenotypic manifestations of Down syndrome are associated with the locus 21q22. The maternal and parental nondisjunction of X-chromosomes in meiosis causes Klinefelter and Turner syndromes. These chromosomal diseases are variants of intersexualism with intermediate chromosomal sex. Down-Klinefelter and Down-Turner syndromes are double aneuploidies. Patients have a Down syndrome phenotype at birth, and signs of Klinefelter and Turner syndromes occur during puberty. Diagnosis of aneuploidy is based on the cytogenetic investigation (karyotyping), DNA analysis, ultrasonography and biochemical markers of chromosomal pathology.

‘The Stuff of Slow Constitution’: Reading Down Syndrome for Race, Disability, and the Timing that Makes Them So

Somatechnics ◽  
2016 ◽  
Vol 6 (2) ◽  
pp. 235-248 ◽  
Author(s):  
Mel Y. Chen
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Historical Perspective ◽  
Early History ◽  
Present Moment ◽  
History Of ◽  
Living Being

In this paper I would like to bring into historical perspective the interrelation of several notions such as race and disability, which at the present moment seem to risk, especially in the fixing language of diversity, being institutionalised as orthogonal in nature to one another rather than co-constitutive. I bring these notions into historical clarity primarily through the early history of what is today known as Down Syndrome or Trisomy 21, but in 1866 was given the name ‘mongoloid idiocy’ by English physician John Langdon Down. In order to examine the complexity of these notions, I explore the idea of ‘slow’ populations in development, the idea of a material(ist) constitution of a living being, the ‘fit’ or aptness of environmental biochemistries broadly construed, and, finally, the germinal interarticulation of race and disability – an ensemble that continues to commutatively enflesh each of these notions in their turn.

Cubilin, the Intrinsic Factor-Vitamin B12 Receptor in Development and Disease

2020 ◽  
Vol 27 (19) ◽  
pp. 3123-3150 ◽  
Author(s):  
Renata Kozyraki ◽  
Olivier Cases
Keyword(s):  
Vitamin B12 ◽  
Cancer Progression ◽  
Intrinsic Factor ◽  
Basic Research ◽  
Toxic Substances ◽  
Human Pathology ◽  
Peripheral Membrane Protein ◽  
Epidermal Growth ◽  
Fgf8 Signaling

Gp280/Intrinsic factor-vitamin B12 receptor/Cubilin (CUBN) is a large endocytic receptor serving multiple functions in vitamin B12 homeostasis, renal reabsorption of protein or toxic substances including albumin, vitamin D-binding protein or cadmium. Cubilin is a peripheral membrane protein consisting of 8 Epidermal Growth Factor (EGF)-like repeats and 27 CUB (defined as Complement C1r/C1s, Uegf, BMP1) domains. This structurally unique protein interacts with at least two molecular partners, Amnionless (AMN) and Lrp2/Megalin. AMN is involved in appropriate plasma membrane transport of Cubilin whereas Lrp2 is essential for efficient internalization of Cubilin and its ligands. Observations gleaned from animal models with Cubn deficiency or human diseases demonstrate the importance of this protein. In this review addressed to basic research and medical scientists, we summarize currently available data on Cubilin and its implication in renal and intestinal biology. We also discuss the role of Cubilin as a modulator of Fgf8 signaling during embryonic development and propose that the Cubilin-Fgf8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects. We finally provide experimental elements suggesting that some aspects of Cubilin physiology might be relevant in drug design.

scholarly journals Characterization of Caenorhabditis elegans Homologs of the Down Syndrome Candidate Gene DYRK1A

Genetics ◽  
2003 ◽  
Vol 163 (2) ◽  
pp. 571-580 ◽  
Author(s):  
William B Raich ◽  
Celine Moorman ◽  
Clay O Lacefield ◽  
Jonah Lehrer ◽  
Dusan Bartsch ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Caenorhabditis Elegans ◽  
Trisomy 21 ◽  
Gene Dosage ◽  
Inducible Promoters ◽  
C Elegans ◽  
Dual Specificity ◽  
Specificity Protein

Abstract The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.

scholarly journals Medical vulnerability of individuals with Down syndrome to severe COVID-19–data from the Trisomy 21 Research Society and the UK ISARIC4C survey

2021 ◽  
Vol 33 ◽  
pp. 100769 ◽  
Author(s):  
Anke Hüls ◽  
Alberto C.S. Costa ◽  
Mara Dierssen ◽  
R. Asaad Baksh ◽  
Stefania Bargagna ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Research Society ◽  
The Uk

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 Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles

2020 ◽  
Author(s):  
Benjamin I Laufer ◽  
Hyeyeon Hwang ◽  
Julia M Jianu ◽  
Charles E Mordaunt ◽  
Ian F Korf ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Down Syndrome ◽  
Early Life ◽  
Trisomy 21 ◽  
Bisulfite Sequencing ◽  
Dried Blood Spots ◽  
Whole Genome ◽  
Genome Wide ◽  
Low Pass ◽  
Genome Bisulfite Sequencing

Abstract Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example of genetics shaping epigenetics, as multiple array-based studies have demonstrated that trisomy 21 is characterized by genome-wide alterations to DNA methylation. By assaying over 24 million CpG sites, thousands of genome-wide significant (q < 0.05) differentially methylated regions (DMRs) that distinguished DS from typical development and idiopathic developmental delay were identified. Machine learning feature selection refined these DMRs to 22 loci. The DS DMRs mapped to genes involved in neurodevelopment, metabolism, and transcriptional regulation. Based on comparisons with previous DS methylation studies and reference epigenomes, the hypermethylated DS DMRs were significantly (q < 0.05) enriched across tissues while the hypomethylated DS DMRs were significantly (q < 0.05) enriched for blood-specific chromatin states. A ~28 kb block of hypermethylation was observed on chromosome 21 in the RUNX1 locus, which encodes a hematopoietic transcription factor whose binding motif was the most significantly enriched (q < 0.05) overall and specifically within the hypomethylated DMRs. Finally, we also identified DMRs that distinguished DS NDBS based on the presence or absence of congenital heart disease (CHD). Together, these results not only demonstrate the utility of low-pass WGBS on NDBS samples for epigenome-wide association studies, but also provide new insights into the early life mechanisms of epigenomic dysregulation resulting from trisomy 21.

scholarly journals Investigating the Link Between Trisomy 21 and Acquired Mutations in the GATA1 Gene

The Physician ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. c9
Author(s):  
Triya Chakravorty ◽  
Irene Roberts
Keyword(s):  
Down Syndrome ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Trisomy 21 ◽  
Children With Down Syndrome ◽  
Transient Abnormal Myelopoiesis ◽  
Increased Risk ◽  
Leukaemic Cells ◽  
Acute Myeloid

Children with Down syndrome (DS) due to trisomy 21 (T21) are at an increased risk of developing the neonatal preleukaemic disorder transient abnormal myelopoiesis (TAM), which may transform into childhood acute myeloid leukaemia (ML-DS). Leukaemic cells in TAM and ML-DS have acquired mutations in the GATA1 gene. Although it is clear that acquired mutations in GATA1 are necessary for the development of TAM and ML-DS, questions remain concerning the mechanisms of disease.

scholarly journals Polymorphisms of the MTHFR gene in mothers of children with trisomy 21 (Down syndrome) in a Polish population

2020 ◽  
Vol 29 (2) ◽  
pp. 251-256
Author(s):  
Paulina Czechowicz ◽  
Małgorzata Małodobra-Mazur ◽  
Arleta Lebioda ◽  
Anna Jonkisz ◽  
Tadeusz Dobosz ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Mthfr Gene ◽  
Polish Population

Acquired Chromosome Rearrangements, Including Fine Interstitial Deletions, in a Patient with Down Syndrome and Monoblastic Leukemia

PEDIATRICS ◽  
1984 ◽  
Vol 74 (6) ◽  
pp. 1029-1033
Author(s):  
Shinichi Misawa ◽  
Joseph R. Testa ◽  
Lewis C. Strauss ◽  
Richard D. Leavitt ◽  
Curt I. Civin
Keyword(s):  
Down Syndrome ◽  
Acute Leukemia ◽  
Trisomy 21 ◽  
Female Child ◽  
Chromosome Rearrangements ◽  
Leukemic Cells ◽  
Structural Rearrangements ◽  
Time Analysis ◽  
Acute Monoblastic Leukemia ◽  
Cytogenetic Studies

A female child with Down syndrome who developed acute monoblastic leukemia is reported. Anemia associated with milk leukopenia was first recognized when the patient was 14 months old. Acute monoblastic leukemia was diagnosed 1 year later; cytogenetic studies were performed on circulating leukemic cells at this time. Analysis of elongated, finely banded chromosomes revealed three structural rearrangements, including two rather subtle interstitial deletions, in addition to trisomy 21 which was representative of the patient's constitutional karyotype. The karyotype of the leukemic cells was 47,XX,+21,t(3;18)(p23;q11.2), del(7)(q31.1q31.3), del(9)(p22p24 or p21p23). The patient received no cytostatic chemotherapy and died 4 months after the diagnosis of acute leukemia was made.

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