down syndrome

Summary

Summary: A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe MENTAL RETARDATION. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)

Top Publications

  1. pmc Amyloid plaque core protein in Alzheimer disease and Down syndrome
    C L Masters
    Proc Natl Acad Sci U S A 82:4245-9. 1985
  2. ncbi DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study
    Glenn E Palomaki
    Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
    Genet Med 13:913-20. 2011
  3. pmc DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study
    Glenn E Palomaki
    Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA
    Genet Med 14:296-305. 2012
  4. pmc Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study
    Rossa W K Chiu
    Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
    BMJ 342:c7401. 2011
  5. pmc miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia
    Jan Henning Klusmann
    Children s Hospital Boston, Massachusetts 02115, USA
    Genes Dev 24:478-90. 2010
  6. ncbi Gene expression profiling in the adult Down syndrome brain
    H E Lockstone
    Institute of Biotechnology, University of Cambridge, Cambridge, UK
    Genomics 90:647-60. 2007
  7. ncbi Down syndrome and hospitalizations due to respiratory syncytial virus: a population-based study
    Philip Zachariah
    Department of Pediatrics, University of Colorado, Denver, CO, USA
    J Pediatr 160:827-31.e1. 2012
  8. pmc Meta-analysis of heterogeneous Down Syndrome data reveals consistent genome-wide dosage effects related to neurological processes
    Mireia Vilardell
    Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
    BMC Genomics 12:229. 2011
  9. pmc p53 downregulates Down syndrome-associated DYRK1A through miR-1246
    Yu Zhang
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine Simon Cancer Center, 635 Barnhill Drive, MS4053, Indianapolis, Indiana 46202, USA
    EMBO Rep 12:811-7. 2011
  10. pmc Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening
    Maria Loane
    Institute of Nursing Research, University of Ulster, Jordanstown, UK
    Eur J Hum Genet 21:27-33. 2013

Research Grants

  1. Genome-wide recombination as a risk factor for nondisjunction
    NATASHA D HOLLIS; Fiscal Year: 2010
  2. Regulation of AKAP79 Postsynaptic Membrane Targeting
    MARK L DELL'ACQUA; Fiscal Year: 2012
  3. Chromosomal Control of Segregation of C. Elegans
    Abby F Dernburg; Fiscal Year: 2013
  4. Multiple Mechanisms of Nasal Chemoreception
    Diego Restrepo; Fiscal Year: 2012
  5. NFAT Signaling and Down Syndrome
    Gerald R Crabtree; Fiscal Year: 2012
  6. Molecular Analysis of Pericentric Sister Chromatid Cohesion
    PAUL CONNOR MEGEE; Fiscal Year: 2013
  7. Molecular Basis of Nuchal Edema
    Young Kwon Hong; Fiscal Year: 2013
  8. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    Nancy M Hollingsworth; Fiscal Year: 2013
  9. Checkpoints and double strand breaks in S. pombe meiosis
    Susan L Forsburg; Fiscal Year: 2013
  10. Cardiometabolic Risk Factors and Obesity in Adolescents with Down Syndrome
    Sheela Natesh Magge; Fiscal Year: 2013

Detail Information

Publications387 found, 100 shown here

  1. pmc Amyloid plaque core protein in Alzheimer disease and Down syndrome
    C L Masters
    Proc Natl Acad Sci U S A 82:4245-9. 1985
    ..the cerebral amyloid protein that forms the plaque core in Alzheimer disease and in aged individuals with Down syndrome. The protein consists of multimeric aggregates of a polypeptide of about 40 residues (4 kDa)...
  2. ncbi DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study
    Glenn E Palomaki
    Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
    Genet Med 13:913-20. 2011
    Prenatal screening for Down syndrome has improved, but the number of resulting invasive diagnostic procedures remains problematic. Measurement of circulating cell-free DNA in maternal plasma might offer improvement.
  3. pmc DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study
    Glenn E Palomaki
    Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA
    Genet Med 14:296-305. 2012
    ..To determine whether maternal plasma cell-free DNA sequencing can effectively identify trisomy 18 and 13...
  4. pmc Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study
    Rossa W K Chiu
    Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
    BMJ 342:c7401. 2011
    ..To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling...
  5. pmc miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia
    Jan Henning Klusmann
    Children s Hospital Boston, Massachusetts 02115, USA
    Genes Dev 24:478-90. 2010
    Children with trisomy 21/Down syndrome (DS) are at high risk to develop acute megakaryoblastic leukemia (DS-AMKL) and the related transient leukemia (DS-TL)...
  6. ncbi Gene expression profiling in the adult Down syndrome brain
    H E Lockstone
    Institute of Biotechnology, University of Cambridge, Cambridge, UK
    Genomics 90:647-60. 2007
    The mechanisms by which trisomy 21 leads to the characteristic Down syndrome (DS) phenotype are unclear...
  7. ncbi Down syndrome and hospitalizations due to respiratory syncytial virus: a population-based study
    Philip Zachariah
    Department of Pediatrics, University of Colorado, Denver, CO, USA
    J Pediatr 160:827-31.e1. 2012
    To assess the risk estimates for respiratory syncytial virus (RSV) hospitalization in children with Down syndrome (DS) and the clinical features and severity of RSV lower respiratory tract infection (LRTI) in hospitalized children.
  8. pmc Meta-analysis of heterogeneous Down Syndrome data reveals consistent genome-wide dosage effects related to neurological processes
    Mireia Vilardell
    Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
    BMC Genomics 12:229. 2011
    b>Down syndrome (DS; trisomy 21) is the most common genetic cause of mental retardation in the human population and key molecular networks dysregulated in DS are still unknown...
  9. pmc p53 downregulates Down syndrome-associated DYRK1A through miR-1246
    Yu Zhang
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine Simon Cancer Center, 635 Barnhill Drive, MS4053, Indianapolis, Indiana 46202, USA
    EMBO Rep 12:811-7. 2011
    ..response to DNA damage, p53 induces the expression of miR-1246 which, in turn, reduces the level of DYRK1A, a Down syndrome-associated protein kinase. Knockdown of p53 has the opposite effect...
  10. pmc Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening
    Maria Loane
    Institute of Nursing Research, University of Ulster, Jordanstown, UK
    Eur J Hum Genet 21:27-33. 2013
    ..Live birth prevalence has remained stable overall. Differences in prenatal screening and termination between countries lead to wide variation in live birth prevalence...
  11. pmc Trisomy correction in Down syndrome induced pluripotent stem cells
    Li B Li
    Department of Medicine, University of Washington, Seattle, WA 98195, USA
    Cell Stem Cell 11:615-9. 2012
    Human trisomies can alter cellular phenotypes and produce congenital abnormalities such as Down syndrome (DS)...
  12. ncbi Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population
    Kypros H Nicolaides
    Harris Birthright Research Centre for Fetal Medicine, King s College Hospital, King s College, London, England, UK
    Am J Obstet Gynecol 207:374.e1-6. 2012
    ..We sought to assess performance of noninvasive prenatal testing for fetal trisomy in a routinely screened first-trimester pregnancy population...
  13. ncbi α-Tocopherol suppresses lipid peroxidation and behavioral and cognitive impairments in the Ts65Dn mouse model of Down syndrome
    Mototada Shichiri
    Health Research Institute, National Institute of Advanced Industrial Science and Technology, Ikeda, Osaka 563 8577, Japan
    Free Radic Biol Med 50:1801-11. 2011
    It is widely accepted that oxidative stress is involved in the pathogenesis of Down syndrome, but the effectiveness of antioxidant treatment remains inconclusive...
  14. pmc An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes
    Aideen O'Doherty
    Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Science 309:2033-7. 2005
    ..This "transchromosomic" mouse line, Tc1, is a model of trisomy 21, which manifests as Down syndrome (DS) in humans, and has phenotypic alterations in behavior, synaptic plasticity, cerebellar neuronal number, ..
  15. ncbi Reducing GABAA α5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of down syndrome
    Carmen Martínez-Cué
    Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, E 39011 Santander, Spain
    J Neurosci 33:3953-66. 2013
    b>Down syndrome (DS) is associated with neurological complications, including cognitive deficits that lead to impairment in intellectual functioning...
  16. pmc Neurological phenotypes for Down syndrome across the life span
    Ira T Lott
    Department of Pediatrics and Neurology, School of Medicine, University of California Irvine UCI, Orange, CA, USA
    Prog Brain Res 197:101-21. 2012
    This chapter reviews the neurological phenotype of Down syndrome (DS) in early development, childhood, and aging...
  17. pmc Deficits in cognition and synaptic plasticity in a mouse model of Down syndrome ameliorated by GABAB receptor antagonists
    Alexander M Kleschevnikov
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA
    J Neurosci 32:9217-27. 2012
    Cognitive impairment in Down syndrome (DS) is characterized by deficient learning and memory...
  18. pmc Abnormal expression of synaptic proteins and neurotrophin-3 in the Down syndrome mouse model Ts65Dn
    G Pollonini
    Department of Neuroscience, Box 1065, Mount Sinai School of Medicine, New York, NY 10029, USA
    Neuroscience 156:99-106. 2008
    b>Down syndrome (DS) results from triplication of the whole or distal part of human chromosome 21...
  19. pmc Age-dependent dysregulation of brain amyloid precursor protein in the Ts65Dn Down syndrome mouse model
    Jennifer H K Choi
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Neurochem 110:1818-27. 2009
    Individuals with Down syndrome develop beta-amyloid deposition characteristic of early-onset Alzheimer's disease (AD) in mid-life, presumably because of an extra copy of the chromosome 21-located amyloid precursor protein (App) gene...
  20. pmc The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies
    Jan O Korbel
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 106:12031-6. 2009
    b>Down syndrome (DS), or trisomy 21, is a common disorder associated with several complex clinical phenotypes...
  21. pmc Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse lines: relevance for modeling Down syndrome
    Arnaud Duchon
    Institut de Génétique Biologie Moléculaire et Cellulaire, Translational Medicine and Neuroscience Program, Universite de Strasbourg, Illkirch, France
    Mamm Genome 22:674-84. 2011
    b>Down syndrome (DS) is the most frequent genetic disorder leading to intellectual disabilities and is caused by three copies of human chromosome 21...
  22. pmc Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21
    Elisavet A Papageorgiou
    Cytogenetics and Genomics Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
    Nat Med 17:510-3. 2011
    ..The application of this fetal-specific methylation ratio approach provided correct diagnosis of 14 trisomy 21 and 26 normal cases...
  23. pmc Increased efficiency of the GABAA and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome
    Alexander M Kleschevnikov
    Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Neurobiol Dis 45:683-91. 2012
    Cognitive impairment in Down syndrome (DS) involves the hippocampus. In the Ts65Dn mouse model of DS, deficits in hippocampus-dependent learning and synaptic plasticity were linked to enhanced inhibition...
  24. ncbi Early pharmacotherapy restores neurogenesis and cognitive performance in the Ts65Dn mouse model for Down syndrome
    Patrizia Bianchi
    Department of Human and General Physiology, University of Bologna, I 40126 Bologna, Italy
    J Neurosci 30:8769-79. 2010
    b>Down syndrome (DS) is a genetic pathology characterized by intellectual disability and brain hypotrophy...
  25. ncbi Down syndrome: a novel risk factor for respiratory syncytial virus bronchiolitis--a prospective birth-cohort study
    Beatrijs L P Bloemers
    Division of Infectious Diseases, University Medical Centre Utrecht, Department of Pediatrics, 3508 AB, Utrecht, The Netherlands
    Pediatrics 120:e1076-81. 2007
    ..Although Down syndrome is associated with a high risk of respiratory tract infections, little is known about the incidence of ..
  26. ncbi Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group
    Libi Hertzberg
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Blood 115:1006-17. 2010
    ..analyses to elucidate the molecular characteristics of acute lymphoblastic leukemia (ALL) in children with Down syndrome (DS)...
  27. ncbi Frontal cortex BDNF levels correlate with working memory in an animal model of Down syndrome
    Heather A Bimonte-Nelson
    Department of Physiology and Neuroscience and the Center for Studies on Aging, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
    Behav Brain Res 139:47-57. 2003
    Individuals with Down syndrome (DS) develop most neuropathological hallmarks of Alzheimer's disease early in life, including loss of cholinergic markers in the basal forebrain...
  28. ncbi Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of Down syndrome
    Pavel V Belichenko
    Department of Neurology and Neurological Sciences, the Center for Research and Treatment of Down Syndrome and Neuroscience Institute at Stanford University, Stanford, California 94305 5489, USA
    J Comp Neurol 512:453-66. 2009
    b>Down syndrome (DS) is a neurological disorder causing impaired learning and memory. Partial trisomy 16 mice (Ts65Dn) are a genetic model for DS...
  29. pmc A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions
    Tao Yu
    Genetics Program and Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Hum Mol Genet 19:2780-91. 2010
    b>Down syndrome (DS) is caused by the presence of an extra copy of human chromosome 21 (Hsa21) and is the most common genetic cause for developmental cognitive disability...
  30. ncbi The neuropsychology of Down syndrome: evidence for hippocampal dysfunction
    Bruce F Pennington
    Department of Psychology, University of Denver CO 80208, USA
    Child Dev 74:75-93. 2003
    ..7 years, SD = 2.7) individuals with Down syndrome (DS) compared with 28 (M = 4.9 years, SD = ...
  31. pmc Abnormal microRNA expression in Ts65Dn hippocampus and whole blood: contributions to Down syndrome phenotypes
    Jennifer Keck-Wherley
    Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    Dev Neurosci 33:451-67. 2011
    b>Down syndrome (DS; trisomy 21) is one of the most common genetic causes of intellectual disability, which is attributed to triplication of genes located on chromosome 21...
  32. ncbi Part I: clinical practice guidelines for children with Down syndrome from birth to 12 years
    Susan N Van Cleve
    Down Syndrome Center of Western Pennsylvania, Children s Hospital of Pittsburgh, 15213, USA
    J Pediatr Health Care 20:47-54. 2006
  33. ncbi MNB/DYRK1A as a multiple regulator of neuronal development
    Francisco J Tejedor
    Instituto de Neurociencias, CSIC and Universidad Miguel Hernandez, Alicante, Spain
    FEBS J 278:223-35. 2011
    ..data implicating MNB/DYRK1A in brain development and adult brain function, as well as in neurodegeneration and Down syndrome pathologies. Here we review our current understanding of the neurodevelopmental activity of MNB/DYRK1A...
  34. ncbi Oxidative stress and mitochondrial dysfunction in Down syndrome
    Giovanni Pagano
    Cancer Research Center, Mercogliano, Italy
    Adv Exp Med Biol 724:291-9. 2012
    b>Down syndrome (DS) or trisomy 21 is the genetic disease with highest prevalence displaying phenotypic features that both include neurologic deficiencies and a number of clinical outcomes...
  35. ncbi The landscape of somatic mutations in Down syndrome-related myeloid disorders
    Kenichi Yoshida
    1 Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 2 Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan 3
    Nat Genet 45:1293-9. 2013
    ..proliferation resembling acute megakaryoblastic leukemia (AMKL), mostly affecting perinatal infants with Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting AMKL after spontaneous ..
  36. pmc Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
    Anna Conti
    Dipartimento di Biologia e Patologia Cellulare e Molecolare, University Federico II, Napoli, Italy
    BMC Genomics 8:268. 2007
    The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21) genes...
  37. ncbi DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations
    Jacob A Canick
    Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, RI, USA
    Prenat Diagn 32:730-4. 2012
    Studies on prenatal testing for Down syndrome (trisomy 21), trisomy 18, and trisomy 13 by massively parallel shotgun sequencing (MPSS) of circulating cell free DNA have been, for the most part, limited to singleton pregnancies...
  38. ncbi Deficit of complex I activity in human skin fibroblasts with chromosome 21 trisomy and overproduction of reactive oxygen species by mitochondria: involvement of the cAMP/PKA signalling pathway
    Daniela Valenti
    Istituto di Biomembrane e Bioenergetica, Consiglio Nazionale delle Ricerche, 70126 Bari, Italy
    Biochem J 435:679-88. 2011
    ..Taken together, the results of the present study suggest that the drastic decrease in basal cAMP levels observed in DS-HSFs participates in the complex I deficit and overproduction of ROS by DS-HSF mitochondria...
  39. ncbi Impairment of methyl cycle affects mitochondrial methyl availability and glutathione level in Down's syndrome
    Vittoria Infantino
    Department of Chemistry, University of Basilicata, 85100 Potenza, Italy
    Mol Genet Metab 102:378-82. 2011
    ..The possible role of methylation in mitochondria is discussed and some preliminary results on a possible methylation target are presented...
  40. pmc Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation
    Ira T Lott
    Department of Pediatrics, School of Medicine, University of California, Irvine UCI, Orange, California, USA
    Am J Med Genet A 155:1939-48. 2011
    Individuals with Down syndrome over age 40 years are at risk for developing dementia of the Alzheimer type and have evidence for chronic oxidative stress...
  41. ncbi Widespread proliferation impairment and hypocellularity in the cerebellum of fetuses with down syndrome
    Sandra Guidi
    Dipartimento di Fisiologia Umana e Generale, Universita di Bologna, Bologna, Italy
    Brain Pathol 21:361-73. 2011
    Evidence in mouse models for Down syndrome (DS) and human fetuses with DS clearly shows severe neurogenesis impairment in various telencephalic regions, suggesting that this defect may underlie the cognitive abnormalities of DS...
  42. pmc Massive-scale RNA-Seq analysis of non ribosomal transcriptome in human trisomy 21
    Valerio Costa
    Institute of Genetics and Biophysics A Buzzati Traverso, CNR, Naples, Italy
    PLoS ONE 6:e18493. 2011
    Hybridization- and tag-based technologies have been successfully used in Down syndrome to identify genes involved in various aspects of the pathogenesis...
  43. pmc Effects of long-term memantine on memory and neuropathology in Ts65Dn mice, a model for Down syndrome
    Jason Lockrow
    Department of Neuroscience, Center on Aging, Medical University of South Carolina, 173 Ashley Avenue, Ste 410D, Charleston, SC 29425, USA
    Behav Brain Res 221:610-22. 2011
    ..The present study assessed the effects of both short- and long-term memantine treatment in a mouse model of Down syndrome (DS), the Ts65Dn mouse...
  44. pmc Transcript level alterations reflect gene dosage effects across multiple tissues in a mouse model of down syndrome
    Pascal Kahlem
    Max Planck Institute for Molecular Genetics, D 14195, Berlin, Germany
    Genome Res 14:1258-67. 2004
    Human trisomy 21, which results in Down syndrome (DS), is one of the most complicated congenital genetic anomalies compatible with life, yet little is known about the molecular basis of DS...
  45. ncbi Activation of the Notch pathway in Down syndrome: cross-talk of Notch and APP
    David F Fischer
    Netherlands Institute for Brain Research, Amsterdam, The Netherlands
    FASEB J 19:1451-8. 2005
    b>Down syndrome (DS) patients suffer from mental retardation, but also display enhanced beta-APP production and develop cortical amyloid plaques at an early age...
  46. ncbi Beta-amyloid, oxidative stress and down syndrome
    Ira T Lott
    Department of Pediatrics and Neurology, Alzheimer Disease Research Center, University of California, Irvine, School of Medicine, Irvine, California 92868, USA
    Curr Alzheimer Res 3:521-8. 2006
    b>Down syndrome (DS) provides a model for studying important aspects of Alzheimer disease (AD). Chromosome 21 contains several genes that have been implicated in neurodegenerative mechanisms...
  47. pmc Infections and immunodeficiency in Down syndrome
    G Ram
    Allergy and Immunology Section, Department of Pediatrics, Baylor College of Medicine, Texas Children s Hospital Houston, Houston, TX, USA
    Clin Exp Immunol 164:9-16. 2011
    b>Down syndrome (DS) is the most common genetic disease and presents with cognitive impairment, cardiac and gastrointestinal abnormalities, in addition to other miscellaneous clinical conditions...
  48. pmc Down's syndrome-like cardiac developmental defects in embryos of the transchromosomic Tc1 mouse
    Louisa Dunlevy
    Division of Developmental Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Cardiovasc Res 88:287-95. 2010
    ..Here, we present analysis of the cardiac malformations exhibited by embryos of the transchromosomic mouse line Tc(Hsa21)1TybEmcf (Tc1) which contains more than 90% of chromosome Hsa21 in addition to the normal diploid mouse genome...
  49. pmc Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome
    Tyler K Best
    Neuroscience Graduate Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, School of Medicine, Bethesda, MD 20814, USA
    Exp Neurol 233:749-57. 2012
    GABAergic dysfunction is implicated in hippocampal deficits of the Ts65Dn mouse model of Down syndrome (DS)...
  50. pmc On the promise of pharmacotherapies targeted at cognitive and neurodegenerative components of Down syndrome
    Alberto C S Costa
    Division of Clinical Pharmacology and Toxicology, Department of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA
    Dev Neurosci 33:414-27. 2011
    b>Down syndrome (DS) is the phenotypic consequence of trisomy 21 and is the most common genetically defined cause of intellectual disability. The most complete, widely available, and well-studied animal model of DS is the Ts65Dn mouse...
  51. ncbi Acute injections of the NMDA receptor antagonist memantine rescue performance deficits of the Ts65Dn mouse model of Down syndrome on a fear conditioning test
    Alberto C S Costa
    Division of Clinical Pharmacology and Toxicology, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA
    Neuropsychopharmacology 33:1624-32. 2008
    Individuals with Down syndrome (DS) and Ts65Dn mice (a major animal model of DS) carry an extra copy of the DSCR1 (Down Syndrome Critical Region 1) gene, which encodes for a protein that inhibits calcineurin...
  52. pmc Altered DNA methylation in leukocytes with trisomy 21
    Kristi Kerkel
    Institute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA
    PLoS Genet 6:e1001212. 2010
    The primary abnormality in Down syndrome (DS), trisomy 21, is well known; but how this chromosomal gain produces the complex DS phenotype, including immune system defects, is not well understood...
  53. ncbi An increase in basal BDNF provokes hyperactivation of the Akt-mammalian target of rapamycin pathway and deregulation of local dendritic translation in a mouse model of Down's syndrome
    José Antonio Troca-Marín
    Departamento de Fisiologia Medica y Biofisica, Universidad de Sevilla, Sevilla, E 41009, Spain
    J Neurosci 31:9445-55. 2011
    ..Together, these findings help elucidate the mechanisms underlying altered synaptic plasticity in DS...
  54. ncbi Quantitative PCR genotyping assay for the Ts65Dn mouse model of Down syndrome
    Dong P Liu
    Jackson Laboratory, Bar Harbor, ME, USA
    Biotechniques 35:1170-4, 1176, 1178 passim. 2003
    The Ts65Dn mouse is a segmentally trisomic model for Down syndrome. Until now, Ts65Dn mice have been identified by the laborious methods of either chromosomal analysis of cultured peripheral lymphocytes or fluorescent in situ ..
  55. ncbi Moyamoya syndrome associated with Down syndrome: outcome after surgical revascularization
    Andrew Jea
    Department of Neurosurgery, Childrens Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    Pediatrics 116:e694-701. 2005
    ..radiologic, and angiographic features of moyamoya syndrome in a surgical series of children and adults with Down syndrome. We wished to define the features of moyamoya syndrome associated with Down syndrome and to determine the ..
  56. pmc Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice
    Tao Yu
    Genetics Program and Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Brain Res 1366:162-71. 2010
    As the genomic basis for Down syndrome (DS), human trisomy 21 is the most common genetic cause of intellectual disability in children and young people...
  57. ncbi Maternal plasma DNA analysis with massively parallel sequencing by ligation for noninvasive prenatal diagnosis of trisomy 21
    Rossa W K Chiu
    Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, Hong Kong SAR, China
    Clin Chem 56:459-63. 2010
    ..The quantification of several other human chromosomes, including chromosomes 18 and 13, has been shown to be less precise, however, with quantitative biases related to the chromosomal GC content...
  58. ncbi Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting
    Mathias Ehrich
    Sequenom Inc, 3595 John Hopkins Ct, San Diego, CA 92121, USA
    Am J Obstet Gynecol 204:205.e1-11. 2011
    ..We sought to evaluate a multiplexed massively parallel shotgun sequencing assay for noninvasive trisomy 21 detection using circulating cell-free fetal DNA...
  59. ncbi Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome "critical region"
    W J Song
    Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Genomics 38:331-9. 1996
    ..2, causes many phenotypes in Down syndrome, including mental retardation...
  60. pmc Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model
    Jason Lockrow
    Department of Neuroscience, and the Center on Aging, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
    Exp Neurol 216:278-89. 2009
    b>Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain...
  61. pmc Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome
    Micaela Galante
    Laboratoire de Pharmacologie de la Synapse, CNRS UMR 8619, Universite Paris Sud, 91405 Orsay Cedex, France
    Hum Mol Genet 18:1449-63. 2009
    b>Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of human chromosome 21 (Hsa21). Recently, O'Doherty et al. [An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes...
  62. pmc Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome
    Louise E Reynolds
    Adhesion and Angiogenesis Laboratory, Barts Institute of Cancer, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK
    Nature 465:813-7. 2010
    ....
  63. ncbi Neurogenesis impairment and increased cell death reduce total neuron number in the hippocampal region of fetuses with Down syndrome
    Sandra Guidi
    Dipartimento di Fisiologia Umana e Generale, Universita di Bologna, Bologna, Italy
    Brain Pathol 18:180-97. 2008
    We previously obtained evidence for reduced cell proliferation in the dentate gyrus (DG) of fetuses with Down syndrome (DS), suggesting that the hippocampal hypoplasia seen in adulthood may be caused by defective early neuron production...
  64. ncbi Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes
    L E Olson
    Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Dev Dyn 230:581-9. 2004
    Two mouse models are widely used for Down syndrome (DS) research. The Ts65Dn mouse carries a small chromosome derived primarily from mouse chromosome 16, causing dosage imbalance for approximately half of human chromosome 21 orthologs...
  65. pmc Digital PCR for the molecular detection of fetal chromosomal aneuploidy
    Y M Dennis Lo
    Li Ka Shing Institute of Health Sciences, Department of Chemical Pathology, School of Public Health, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong Special Administrative Region, People s Republic of China
    Proc Natl Acad Sci U S A 104:13116-21. 2007
    ..We applied the sequential probability ratio test to interpret the digital PCR data. Computer simulation and empirical validation confirmed the high accuracy of the disease classification algorithm...
  66. pmc Trisomy 21 and early brain development
    Tarik F Haydar
    Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA
    Trends Neurosci 35:81-91. 2012
    Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS). The finished human genome sequence provides a thorough catalog of the genetic elements whose altered dosage perturbs development and function in DS...
  67. ncbi A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart
    J J Fuentes
    Molecular Genetics Department, Hospital Duran i Reynals, L Hospitalet de Liobregat, Barcelona, Spain
    Hum Mol Genet 4:1935-44. 1995
    b>Down syndrome is a major cause of mental retardation and congenital heart defects. While most of the affected individuals have three copies of chromosome 21, patients with partial trisomy 21 have also been described...
  68. pmc Molecular characterization of the translocation breakpoints in the Down syndrome mouse model Ts65Dn
    Laura G Reinholdt
    The Jackson Laboratory, Genetic Resource Science, ME, 04609, USA
    Mamm Genome 22:685-91. 2011
    Ts65Dn is a mouse model of Down syndrome: a syndrome that results from chromosome (Chr) 21 trisomy and is associated with congenital defects, cognitive impairment, and ultimately Alzheimer's disease...
  69. pmc Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations
    A M Cataldo
    Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
    Am J Pathol 157:277-86. 2000
    ..In Down syndrome, early endosomes were significantly enlarged in some pyramidal neurons as early as 28 weeks of gestation, ..
  70. ncbi The neuropsychological basis of hypersociability in Williams and Down syndrome
    Melanie A Porter
    Macquarie Centre for Cognitive Science, Macquarie University, NSW 2109, Australia
    Neuropsychologia 45:2839-49. 2007
    ..People with Down syndrome (DS) can also do so, but to a lesser degree...
  71. pmc Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome
    Kate A Alford
    Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, London, UK
    Blood 115:2928-37. 2010
    Trisomy of human chromosome 21 (Hsa21) results in Down syndrome (DS), a disorder that affects many aspects of physiology, including hematopoiesis...
  72. pmc Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice
    J Braudeau
    Centre de Recherche de l Institut du Cerveau et de Moelle épinière, CNRS UMR7225, INSERM UMRS 975, UPMC, Paris, France
    J Psychopharmacol 25:1030-42. 2011
    ..and excitatory neurotransmission has been proposed to contribute to altered brain function in individuals with Down syndrome (DS)...
  73. ncbi Protein expression of BACE1, BACE2 and APP in Down syndrome brains
    M S Cheon
    Department of Pediatrics, Medical University of Vienna, Vienna, Austria
    Amino Acids 35:339-43. 2008
    b>Down syndrome (DS) is the most common human chromosomal abnormality caused by an extra copy of chromosome 21...
  74. ncbi Mitochondrial dysfunction in some oxidative stress-related genetic diseases: Ataxia-Telangiectasia, Down Syndrome, Fanconi Anaemia and Werner Syndrome
    Federico V Pallardo
    Department of Physiology, University of Valencia, CIBERER, Spain
    Biogerontology 11:401-19. 2010
    ..published evidence for the involvement of oxidative stress in the phenotypes of Ataxia-Telangiectasia (A-T), Down Syndrome (DS), Fanconi Anaemia (FA), and Werner Syndrome (WS), from the viewpoint of mitochondrial dysfunction...
  75. ncbi Mouse models of cognitive disorders in trisomy 21: a review
    Zohra Seregaza
    Génomique fonctionnelle, Pathologies, Comportements, P3M, UMR 6196, CNRS Université de la Méditerranée, Marseille, France
    Behav Genet 36:387-404. 2006
    ..This review confirms the crucial but not exclusive contribution of the D21S17-ETS2 region encompassing 16 genes to cognitive disorders...
  76. pmc Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities
    H Sago
    Department of Pediatrics, University of California, Box 0546, San Francisco, CA 94143 0546, USA
    Proc Natl Acad Sci U S A 95:6256-61. 1998
    A mouse model for Down syndrome, Ts1Cje, has been developed...
  77. pmc Longitudinal study of thyroid function in Down's syndrome in the first two decades
    P A Gibson
    Department of Paediatrics, Royal Lancaster Infirmary, Lancaster, UK
    Arch Dis Child 90:574-8. 2005
    ..4 years). At the second test two were hypothyroid and two with isolated raised thyroid stimulating hormone (IR-TSH) were receiving thyroxine...
  78. ncbi Ethnic differences in determinants of participation and non-participation in prenatal screening for Down syndrome: a theoretical framework
    Mirjam P Fransen
    Department of Public Health, Erasmus MC, Rotterdam, The Netherlands
    Prenat Diagn 27:938-50. 2007
    To develop a theoretical framework for analysing ethnic differences in determinants of participation and non-participation in prenatal screening for Down syndrome.
  79. pmc Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: a report from the National Down Syndrome Project
    NATASHA D HOLLIS
    Department of Human Genetics, Emory University, Atlanta, Georgia 30322, USA
    Am J Med Genet A 161:438-44. 2013
    ..Using questionnaire data from the National Down Syndrome Project, a population-based case-control study, we compared the use of folic acid-containing supplements among ..
  80. pmc Lithium rescues synaptic plasticity and memory in Down syndrome mice
    Andrea Contestabile
    Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy
    J Clin Invest 123:348-61. 2013
    b>Down syndrome (DS) patients exhibit abnormalities of hippocampal-dependent explicit memory, a feature that is replicated in relevant mouse models of the disease...
  81. ncbi Variation over time in medical conditions and health service utilization of children with Down syndrome
    Kelly Thomas
    Department of Occupational Therapy, School of Exercise, Biomedical, and Health Sciences, Edith Cowan University, West Perth, Western Australia
    J Pediatr 158:194-200.e1. 2011
    To compare the prevalence of parent reported medical conditions and rates of health service utilization in school-aged children with Down syndrome in Western Australia in 1997 and 2004.
  82. ncbi Down syndrome: the brain in trisomic mode
    Mara Dierssen
    Genes and Disease Programme, Centre for Genomic Regulation CRG, Universitat Pompeu Fabra, Centro de Investigación Biomédica en Red de Enfermedades Raras, E 08003 Barcelona, Spain
    Nat Rev Neurosci 13:844-58. 2012
    b>Down syndrome is the most common form of intellectual disability and results from one of the most complex genetic perturbations that is compatible with survival, trisomy 21...
  83. ncbi Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome
    C Pucharcos
    Down Syndrome Research Group, Medical and Molecular Genetics Center, IRO, Hospital Duran i Reynals, Barcelona, Spain
    Eur J Hum Genet 7:704-12. 1999
    ..expression pattern of Intersectin in mouse brain, its presumed function and its overexpression in brains from Down syndrome patients, suggest that Intersectin may contribute in a gene dosage-dependent manner to some of the ..
  84. ncbi DNMT3B promoter polymorphisms and maternal risk of birth of a child with Down syndrome
    Fabio Coppede
    Department of Laboratory Medicine, Pisa University Hospital AOUP, Via S Giuseppe 22, Pisa 56126, Italy
    Hum Reprod 28:545-50. 2013
    Are DNMT3B promoter polymorphisms among maternal risk factors for the birth of a child with Down syndrome (DS)?
  85. pmc Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles
    M G Loudin
    Division of Pediatric Hematology Oncology, Texas Children s Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
    Leukemia 25:1555-63. 2011
    Patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have distinct clinical and biological features...
  86. pmc Cancers and immune related diseases associated with Down's syndrome: a record linkage study
    M J Goldacre
    Unit of Health Care Epidemiology, Department of Health, University of Oxford, Oxford, UK
    Arch Dis Child 89:1014-7. 2004
    ..To determine the risk of cancers and selected immune related diseases in people with Down's syndrome, relative to risk in other people...
  87. pmc Massively parallel sequencing reveals the complex structure of an irradiated human chromosome on a mouse background in the Tc1 model of Down syndrome
    Susan M Gribble
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
    PLoS ONE 8:e60482. 2013
    b>Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome...
  88. ncbi Clinical manifestations of the deletion of Down syndrome critical region including DYRK1A and KCNJ6
    Toshiyuki Yamamoto
    Tokyo Women s Medical University Institute for Integrated Medical Sciences, Tokyo, Japan
    Am J Med Genet A 155:113-9. 2011
    A relatively small region of human chromosome 21 (Hsa21) is considered to play a major role in Down syndrome (DS) phenotypes, and the concept of a Down syndrome critical region (DSCR) has been proposed...
  89. pmc Trisomy for synaptojanin1 in Down syndrome is functionally linked to the enlargement of early endosomes
    Jack Christophe Cossec
    Centre de Recherche de l Institut du Cerveau et de la Moelle, CNRS UMR7225, UPMC, INSERM UMRS975, Hopital Pitie Salpetriere, Paris, France
    Hum Mol Genet 21:3156-72. 2012
    Enlarged early endosomes have been observed in neurons and fibroblasts in Down syndrome (DS). These endosome abnormalities have been implicated in the early development of Alzheimer's disease (AD) pathology in these subjects...
  90. ncbi Lower neonatal screening thyroxine concentrations in down syndrome newborns
    A S P van Trotsenburg
    Department of Pediatric Endocrinology, Emma Children s Hospital AMC, 1105 AZ Amsterdam, The Netherlands
    J Clin Endocrinol Metab 88:1512-5. 2003
    ..neonatal screening programs and a very high prevalence of (mild) plasma TSH elevation in young children with Down syndrome (DS)...
  91. ncbi BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down syndrome patients
    Asma Tlili
    Unit of Functional and Adaptive Biology, Sorbonne Paris Cité, Univ Paris Diderot, EAC CNRS 4413, 75013 Paris, France
    Mol Neurobiol 46:297-303. 2012
    b>Down syndrome or trisomy 21 is the most common genetic disorder leading to mental retardation. One feature is impaired short- and long-term spatial memory, which has been linked to altered brain-derived neurotrophic factor (BDNF) levels...
  92. ncbi Gait dynamics in trisomic mice: quantitative neurological traits of Down syndrome
    Thomas G Hampton
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    Physiol Behav 82:381-9. 2004
    The segmentally trisomic mouse Ts65Dn is a model of Down syndrome (DS). Gait abnormalities are almost universal in persons with DS...
  93. ncbi Over-expression of RCAN1 causes Down syndrome-like hippocampal deficits that alter learning and memory
    Katherine R Martin
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3168 Victoria, Australia
    Hum Mol Genet 21:3025-41. 2012
    People with Down syndrome (DS) exhibit abnormal brain structure. Alterations affecting neurotransmission and signalling pathways that govern brain function are also evident...
  94. pmc Auditory function in the Tc1 mouse model of down syndrome suggests a limited region of human chromosome 21 involved in otitis media
    Stephanie Kuhn
    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    PLoS ONE 7:e31433. 2012
    b>Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media...
  95. ncbi The profile and incidence of cancer in Down syndrome
    S G Sullivan
    School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA, Australia
    J Intellect Disabil Res 51:228-31. 2007
    b>Down syndrome is one of the commonest causes of intellectual disability...
  96. ncbi Effects of combined aerobic and resistance exercise training in adults with and without Down syndrome
    Goncalo V Mendonca
    Center of Human Performance, Technical University of Lisbon, Portugal
    Arch Phys Med Rehabil 92:37-45. 2011
    To determine whether adults with Down syndrome (DS) could improve their submaximal and peak exercise capacity, as for adults without disabilities, after 12 weeks of combined (aerobic and resistance) exercise training.
  97. ncbi Gross motor function of children with down syndrome: creation of motor growth curves
    R J Palisano
    Department of Rehabilitation Sciences, MCP Hahnemann University, Philadelphia, PA 19102 1192, USA
    Arch Phys Med Rehabil 82:494-500. 2001
    To create gross motor function growth curves for children with Down syndrome (DS) and to estimate the probability that motor functions are achieved by different ages.
  98. ncbi DYRK1A-mediated hyperphosphorylation of Tau. A functional link between Down syndrome and Alzheimer disease
    Soo Ryoon Ryoo
    Graduate Program in Neuroscience, Institute for Brain Science and Technology, Inje University, Busan 614 735, South Korea
    J Biol Chem 282:34850-7. 2007
    Most individuals with Down syndrome show early onset of Alzheimer disease (AD), resulting from the extra copy of chromosome 21...
  99. ncbi Maternal cfDNA screening for Down syndrome--a cost sensitivity analysis
    Howard Cuckle
    Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, USA
    Prenat Diagn 33:636-42. 2013
    This study aimed to determine the principal factors contributing to the cost of avoiding a birth with Down syndrome by using cell-free DNA (cfDNA) to replace conventional screening.
  100. pmc Significant effect of APOE epsilon 4 genotype on the risk of dementia in Alzheimer's disease and mortality in persons with Down syndrome
    V P Prasher
    The Greenfields, Monyhull Hospital, Birmingham, UK
    Int J Geriatr Psychiatry 23:1134-40. 2008
    Virtually all adults with Down syndrome (DS) have neuropathological manifestations of Dementia in Alzheimer's disease (DAD) but not all develop clinical psychopathology...
  101. ncbi Serotonin and brain development: role in human developmental diseases
    P M Whitaker-Azmitia
    Program in Biopsychology, Department of Psychology, SUNY at Stony Brook, 11794 2500, USA
    Brain Res Bull 56:479-85. 2001
    ..Disruption of serotonergic development can leave permanent alterations in brain function and behavior. This may be the case in such human developmental illnesses as autism and Down Syndrome.

Research Grants72

  1. Genome-wide recombination as a risk factor for nondisjunction
    NATASHA D HOLLIS; Fiscal Year: 2010
    ..For years, trisomy 21, also known as Down Syndrome (DS), has been used as a model to study human nondisjunction...
  2. Regulation of AKAP79 Postsynaptic Membrane Targeting
    MARK L DELL'ACQUA; Fiscal Year: 2012
    ..cognition in neurological disorders such as Alzheimer's and epilepsy and mental health disorders such as Down syndrome and schizophrenia...
  3. Chromosomal Control of Segregation of C. Elegans
    Abby F Dernburg; Fiscal Year: 2013
    ..of human miscarriages, infertility, and mental retardation arising from chromosomal birth defects such as Down syndrome. Studies of meiosis have yielded insights into fundamental cell processes, including DNA repair, chromosome ..
  4. Multiple Mechanisms of Nasal Chemoreception
    Diego Restrepo; Fiscal Year: 2012
    ..New York: Wiley-Liss), pp. 257-284. Turetsky,B.I., Moberg,P.J., Owzar,K., Johnson,S.C., Doty,R.L., and Gur,R.E. (2003). Physiologic impairment of olfactory stimulus processing in schizophrenia. Biol. Psychiatry 53, 403-411. ..
  5. NFAT Signaling and Down Syndrome
    Gerald R Crabtree; Fiscal Year: 2012
    ..most common human aneuploidy is complete or partial trisomy of human chromosome 21 (HSA21), which results in Down Syndrome (DS). Trisomy 21 occurs at a frequency of 1 in 43 spontaneous abortions and 1 in 750 live births...
  6. Molecular Analysis of Pericentric Sister Chromatid Cohesion
    PAUL CONNOR MEGEE; Fiscal Year: 2013
    ..cells during each cell division, and errors in these events can lead to cancer or genetic disease, such as Down syndrome. The accurate segregation of replicated chromosomes, or sister chromatids, to daughter cells requires that ..
  7. Molecular Basis of Nuchal Edema
    Young Kwon Hong; Fiscal Year: 2013
    ..Studies show that more than 80% of NE fetuses carry chromosomal abnormalities such as Down syndrome. Although NE has been reported to be associated with disturbed development of the lymphatic system, the ..
  8. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    Nancy M Hollingsworth; Fiscal Year: 2013
    ..In humans, failures in meiosis result in infertility and birth defects such as Trisomy 21 or Down Syndrome. Unique to meiosis is the first meiotic division, in which homologous pairs of sister chromatids segregate to ..
  9. Checkpoints and double strand breaks in S. pombe meiosis
    Susan L Forsburg; Fiscal Year: 2013
    ..during meiosis accounts for as many as 50% of human miscarriages and contributes to birth defects such as Down Syndrome. Maintenance of genome stability during the normal cell cycle is closely tied to DNA replication fork ..
  10. Cardiometabolic Risk Factors and Obesity in Adolescents with Down Syndrome
    Sheela Natesh Magge; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): More than 400,000 people living in the US have Down syndrome, a congenital disorder arising from the presence of three, rather than two, copies of chromosome 21...
  11. microRNA and Down Syndrome
    Karl H Obrietan; Fiscal Year: 2010
    The chromosome abnormality in Down syndrome (DS) results from a triplication in a portion of human chromosome 21 (Hsa21), but how this chromosomal anomaly causes the DS phenotype is not clear...
  12. MRDD Research Center
    KARL PFENNINGER; Fiscal Year: 2009
    ..The second area of strength is in exploring the genes responsible for single and multigene disorders: autism, Down syndrome, fragile X syndrome, dyslexia, attention deficit hyperactivity disorder, and schizophrenia...
  13. Predicting Cognitive Decline in Adults with Down Syndrome
    Ira T Lott; Fiscal Year: 2013
    Project Summary/Abstract The objective of this proposal is to predict cognitive decline in adults with Down syndrome and to ultimately provide a platform for early intervention to prevent the dementia associated with Alzheimer disease...
  14. CONTROL OF MEIOSIS AND GERMLINE PROLIFERATION
    DAVID IRWIN GREENSTEIN; Fiscal Year: 2012
    ..control meiotic progression because chromosome missegregation in female meiosis I is the leading cause of Down syndrome and miscarriage...
  15. Translating Dosage Compensation to Trisomy
    Jeanne Bentley Lawrence; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Down Syndrome is a very common and clinically important genetic disorder, yet it receives very little attention for gene therapy, unlike many less common single-gene disorders...
  16. RAX, PKR and ethanol neurotoxicity
    Gang Chen; Fiscal Year: 2013
    ..of younger school children is recently estimated as high as 2-5% in the United State and is more common than Down syndrome and autism. FASD-related costs are more than $6 billion annually...
  17. Fundamental mechanisms of protein kinase activation loop autophosphorlyation
    Vaughn Cleghon; Fiscal Year: 2013
    ..The DYRK family of kinases for example, plays important roles in Down Syndrome, microcephaly, cancer, and Alzheimer's disease...
  18. Regulation of AKAP79 Postsynaptic Targeting and Signaling
    MARK L DELL'ACQUA; Fiscal Year: 2013
    ..and memory processes that are altered in diseases including post- traumatic stress disorder, schizophrenia, Down syndrome, and Alzheimer's...
  19. Human Pluripotent Stem Cell and Progenitor Models of Cardiac and Blood Diseases
    LEONARD IRA ZON; Fiscal Year: 2013
    ..gene defects into mouse strains has failed to phenocopy cardinal features of diseases like Fanconi anemia and Down Syndrome. Human models would offer a relevant system to study these diseases and to develop therapeutics...
  20. Sensorimotor Control of the Human Orofacial System
    Steven M Barlow; Fiscal Year: 2012
    ..syndrome (RDS), (2) chronic lung disease and/or bronchopulmonary dysplasia (CLD/BPD), and (3) infants with Down syndrome (DS)...
  21. EphB signaling in dendritic spine development
    Iryna M Ethell; Fiscal Year: 2013
    ..with neurodevelopmental disorders associated with mental retardation and autism, including Rett Syndrome, Down Syndrome, Angleman's Syndrome and Fragile X Syndrome, that exhibit immature dendritic spine profiles...
  22. GATA1 Mutation in Defective Erythropoiesis
    John D Crispino; Fiscal Year: 2013
    ..In the presence of trisomy 21, GATA1 mutations that delete the N- terminus lead to Down syndrome associated Acute Megakaryoblastic Leukemia (DS-AMKL)...
  23. Organization and Regulation of Eukaryotic Centromeres
    BETH SULLIVAN; Fiscal Year: 2009
    ..in chromosome inheritance lead to chromosome abnormalities (aneuploidy) that cause many birth defects, such as Down Syndrome and miscarriages, and are the hallmarks of almost all types of cancers...
  24. Developing fluorescent probes for the endogenous gaseous transmitters NO and H2S
    MICHAEL PLUTH; Fiscal Year: 2013
    ..Fluorophores will be derivatized with specially designed protecting groups that can only be removed by H2S. Removal of the fluorophore protecting group will restore the fluorescence, thus forming a turn-on probe for H2S. ..
  25. Synaptonemal complex assembly and function in meiosis
    MONICA P COLAIACOVO; Fiscal Year: 2013
    ..to chromosome nondisjunction, with disastrous consequences including miscarriages and birth defects such as Down syndrome. Our goal is to investigate the roles, macromolecular assembly and regulation of the SC, whose functions are ..
  26. The Down Syndrome Growing Up Study
    Babette S Zemel; Fiscal Year: 2012
    PROJECT SUMMARY Down syndrome (DS) is a common genetic disorder occurring in approximately 1 in 700 births...
  27. Perinatal choline therapy in a mouse model of Down Syndrome &Alzheimer's Disease
    Barbara J Strupp; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): In addition to mental retardation, individuals with Down syndrome (DS) universally develop the neuropathological hallmarks of Alzheimer's Disease (AD) in early adulthood...
  28. Role of PIP2 metabolism imbalance in Down Syndrome
    GILBERT DIPAOLO; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Down syndrome (DS) is the most common cause of mental retardation. In DS, integrated gene expression is altered due to the presence of a third copy of human chromosome 21 (HC21)...
  29. Systems Biology for Studies of Cognition in Down Syndrome
    Katheleen Gardiner; Fiscal Year: 2012
    The incidence of Down syndrome (DS) is one in 700 live births, the life expectancy is now >50 years, and the average IQ is approximately 50. Therefore, DS is a significant social and medical issue...
  30. Role of CDC14B in mouse oocyte maturation
    KAREN A SCHINDLER; Fiscal Year: 2010
    ..The major goal of this proposal is to determine the role for the CDC14B phosphatase during meiosis in females using the mouse model ..
  31. Genetic Basis of Failed Cognition in Young and Aged Mouse Models of Trisomy 21
    Eugene Yu; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Trisomy 21, Down syndrome (DS), affects approximately 400,000 people in the U.S., causing cognitive disability, which includes the neuropathology of Alzheimer's disease and late-life dementia...
  32. A Molecular View of Chromosome Recombination &Segregation in Eukaryotic Meiosis
    KEVIN DANIEL CORBETT; Fiscal Year: 2013
    ..As such, aneuploidy is the leading genetic cause of miscarriage and of mental retardation (e.g. Down syndrome, caused by trisomy of chromosome 21)...
  33. Pupil Size and Circadian Salivary Variations in Autism Spectrum Disorder
    JOHN A COLOMBO; Fiscal Year: 2010
    ..on two separate days on a group of 20 children with a diagnosed Autism Spectrum Disorder, 20 children with Down Syndrome, and 20 typically-developing children...
  34. Using Transport to Map the Brain
    Elaine L Bearer; Fiscal Year: 2010
    ..alterations in this circuit are implicated in cognitive impairment of both Alzheimer's disease (AD) and Down Syndrome (DS)...
  35. Activity-dependent microRNA expression and function in the mature nervous system
    Karl H Obrietan; Fiscal Year: 2013
    ..of microRNAs expression has been suggested to contribute to a number of neurological disorders, including Down syndrome, Rett syndrome and schizophrenia...
  36. Amyloid Plaque and Tangle Imaging in Alzheimer's Disease and Down Syndrome
    Linda D Nelson; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Down syndrome is a model for the study of Alzheimer's disease because almost 100% of middle-aged individuals with this condition show a specific pathogenic process that follows a predictable ..
  37. Molecular Mechanisms of Chromosome Segregation in Yeast
    Jennifer L Gerton; Fiscal Year: 2012
    ..Cancer Res, 2005. 65: p. 4683-9. 3. Heun, P., et al., Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores. Dev Cell, 2006. 10: p. 303-15. ..
  38. Developing and Maintaining Physical Fitness in Adolescents with Down Syndrome
    HEIDI ISABEL STANISH; Fiscal Year: 2011
    ..true for our underserved population of children and adolescents with intellectual disabilities (ID), including Down syndrome (DS) (Whitt-Glover, O'Neill, &Stettler, 2006)...
  39. Functional Characterization of Rec104 in Meiotic Recombination
    Isabel Lam; Fiscal Year: 2012
    ..g., Down syndrome). Accurate segregation of homologous chromosomes depends on a process known as recombination...
  40. Genetic Dissection of Trisomy 21
    Eugene Yu; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Trisomy 21/Down syndrome (DS) is one of the most important human genetic diseases. It currently affects approximately 350,000 people in the United States and more than 2,000,000 people worldwide...
  41. MOLECULAR GENETICS OF RHIZOBIUM NODULATION PLASMIDS
    Graham C Walker; Fiscal Year: 2013
    ..The human homolog of YbeY, C21ORF57, encoded in the Down Syndrome Critical Region of chromosome 21, is also an RNase that is critically required for mitochondrial function in ..
  42. Analysis of checkpoint function in the germ line.
    JoAnne Engebrecht; Fiscal Year: 2010
    ..Our studies are aimed at understanding how errors arise during this process. In humans, such errors result in infertility, pregnancy loss and birth defects such as Down Syndrome.
  43. Penn Center for ELSI Research in Emerging Genetic Technologies in Health Care
    Reed E Pyeritz; Fiscal Year: 2012
    ..The initial studies will be: 1) To explore the evolution of prenatal screening for Down syndrome and cystic fibrosis carrier screening through a collaboration between historians of science, medical ..
  44. Down syndrome: Bridging Genes, Brain and Cognition
    JULIE RUTH KORENBERG; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Down syndrome (DS) or trisomy for chromosome 21, is a major cause of mental retardation and congenital heart disease, that affects more than 400,000 individuals in the USA...
  45. Intersectin Links Amyloidogenic Processes in Alzheimer Disease and Down Syndrome
    Jessica O Wilson; Fiscal Year: 2013
    ..Interestingly, Down Syndrome (DS) patients over the age of 35 invariably develop AD-like neuropathology, suggesting that this variant of AD ..
  46. Protection of Centromeric Cohesion by Bub1 and Sgo1
    Hongtao Yu; Fiscal Year: 2010
    ..research will shed light on the mechanism of chromosome segregation and may in turn lead to better understanding and prevention of chromosomal instability and aneuploidy in human cancers and birth defects, such as Down Syndrome.
  47. 15th International Society for Prenatal Diagnosis Meeting
    Diana W Bianchi; Fiscal Year: 2010
    ..whether conventional karyotyping is necessary in the post-array-CGH era, and whether ultrasound is better for Down syndrome screening than cell-free fetal nucleic acids in maternal blood...
  48. Inhibition of BACE1 for benefiting Alzheimer's patients
    Riqiang Yan; Fiscal Year: 2013
    ..Individuals with Down syndrome (DS), due to an extra copy of chromosome 21 in which APP is located at 21q21, develop age-related cognitive ..
  49. Gene Discovery in Familial Keratoconus
    Yutao Liu; Fiscal Year: 2013
    ..Second, significantly increased prevalence of keratoconus in Down syndrome patients (three copies of chromosome 21) also indicates the role of DNA duplication...
  50. Structural and Functional Specificity of Rab GTPases
    Guangpu Li; Fiscal Year: 2013
    ..signal transduction plays an important role in neurodegenerative diseases such as Alzheimer's disease and Down syndrome. We found that inhibition of Rab22 function via RNAi or dominant negative mutants dramatically reduces NGF-..
  51. Predicting Obstructive Sleep Apnea in Down Syndrome
    BRIAN GARY SKOTKO; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) in individuals with Down syndrome is associated with multiple morbidities: systemic and pulmonary hypertension, glucose intolerance, cardiovascular and cerebrovascular ..
  52. FEEDBACK CONTROL OF THE CELL CYCLE
    Andrew W Murray; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: Cancer and Down syndrome occur because cells lose track of their chromosomes...
  53. GPS Base System :Support Walking Exercise &Health Monitoring for IDD Individual
    Daniel K Davies; Fiscal Year: 2013
    ..provided by applicant): Health disparities between individuals with intellectual disabilities, including Down Syndrome, and the general population are well documented...
  54. Calcineurin/NFAT signaling in pathogenesis of neurodegeneration in Down Syndrome
    Isabella A Graef; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The development of individuals with trisomy 21/ Down Syndrome (DS) is characterized by delayed cognitive development in infancy and childhood leading to mild to moderate mental retardation, followed ..
  55. Identifying and characterizing proteins that detect unpaired DNA during meiosis.
    THOMAS MICHAEL HAMMOND; Fiscal Year: 2013
    ..meiosis can produce gametes with incorrect numbers of chromosomes, leading to disorders such as trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome)...
  56. Identification of Altered Molecular Signature of Down Syndrome iPS Cells
    Marcelo Bento Soares; Fiscal Year: 2010
    ..Children with Down syndrome (DS) show a spectrum of clinical abnormalities, including a remarkable incidence of abnormal hematopoietic ..
  57. Alternative Splicing of the Drosophilia Dscam Pre-mRNA
    Brenton R Graveley; Fiscal Year: 2013
    ..The long term goals of this proposal are to understand how the alternative splicing of the Drosophila Down syndrome cell adhesion molecule (Dscam) gene is regulated and to determine the mechanism by which Dscam alternative ..
  58. The Role of Estrogen in Female Germ Cell Development
    Mary C Gieske; Fiscal Year: 2013
    ..and future studies is to understand the causes of aneuploidy so that miscarriage and birth defects such as Down syndrome can be prevented...
  59. Down Syndrome in Massachusetts: A population-based study of early childhood healt
    Eugene Declercq; Fiscal Year: 2011
    Abstract The survival of children with Down syndrome (DS), one of the most common birth defects, has improved markedly over the past few decades. However, substantial racial/ethnic disparities in survival have been identified...
  60. EFFECTS ON AB ON SYNAPTIC TRANMISSION AND PLASTICITY
    Paul Greengard; Fiscal Year: 2011
    ..Finally, we will use Ts65Dn (Down syndrome mouse model) as well as AD mouse models (as a collaboration with Project 2) to investigate Ap-induced synaptic ..
  61. IGF/IGF1R signaling in hematopoiesis and leukemogenesis
    Zhe Li; Fiscal Year: 2013
    ..b>Down syndrome acute megakaryoblastic leukemia (DS-AMKL) and a related preleukemic condition called transient leukemia (DS- ..
  62. Genome-wide recombination profiles in oocytes with chromosome 21 nondisjunction
    Stephanie L Sherman; Fiscal Year: 2010
    ..For the past 15 years, we have investigated trisomy 21, the leading cause of Down syndrome (DS), as a model to understand human nondisjunction...
  63. GUIDING VISUAL ATTENTION TO ENHANCE DISCRIMINATION LEARNING
    Michael T Carlin; Fiscal Year: 2011
    ..g., Down syndrome, autism)...
  64. DEFINITION AND DEVELOPMENT OF THE PHENOTYPE IN AUTISM
    Sally Rogers; Fiscal Year: 2001
    ..The samples to be studied are 1) 25 multiplex families with idiopathic autism and 25 Down syndrome control families (Project 0002) 2) 40 adults with idiopathic autism, 40 adults with FXS, 40 adults with ..
  65. PRENATAL DOWN SYNDROME SCREENING
    Rachel Fisher; Fiscal Year: 1993
    Approximately 1 in 800 live born babies are found to have Down syndrome (complete or partial trisomy 21) [1]. The risk of delivering a baby with Down syndrome (DS) increases with increasing maternal age [2]...
  66. Rett syndrome: determinants of outcome and burden
    Helen Leonard; Fiscal Year: 2007
    ..impact on resource utilization and the economic and social burden on families and community in comparison with Down syndrome and a normal comparison group...
  67. GENES FOR KERATOCONUS AND OCULAR FEATURES IN TRISOMY 21
    Katherine Bergwerk; Fiscal Year: 2002
    ..attempts will be made to make genotype-phenotype correlations of other eye abnormalities in patients with Down syndrome. Dr...
  68. EXPRESSION OF CYSTATHIONINE SYNTHASE AND HUMAN DISEASE
    JAN KRAUS; Fiscal Year: 1993
    ..a role in three human disease states: homocystinuria; peripheral and cerebral occlusive arterial disease; and Down syndrome. CBS, a central enzyme in eukaryotic sulfur metabolism, is a tetramer of 63 kDa subunit It is encoded in ..
  69. VITAMIN E TRIAL IN PERSONS WITH DOWN SYNDROME
    Arthur Dalton; Fiscal Year: 2009
    ..applicant): Alzheimer disease (AD) continues to be the most serious health problem faced by aging persons with Down syndrome. AD is also a major public health concern in the aging general population...
  70. LANGUAGE DEVELOPMENT IN DOWN SYNDROME CHILDREN
    Robin Chapman; Fiscal Year: 2003
    Children and adolescents with Down syndrome (DS) are reported, variously, to have language skills above (vocabulary comprehension) and below (expressive syntax) their nonverbal mental age; cross-sectional evidence suggests that the ..
  71. Wayfinding Skills of Persons with Down Syndrome
    Edward C Merrill; Fiscal Year: 2010
    b>Down syndrome is the most common genetic syndrome resulting in intellectual disability...
  72. Genetic basis of the neural crest deficit in Down syndrome mice
    Randall J Roper; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Trisomy 21 results in phenotypes collectively referred to as Down syndrome (DS) including facial dysmorphology, a distinguishing feature of individuals with DS...