Open AccessJournal Article
Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype.
Julie R. Korenberg,Hiroko Kawashima,Stefan M. Pulst,Tatsuro Ikeuchi,N. Ogasawara,Kohtaro Yamamoto,Steven A. Schonberg,Ruth West,L. Allen,Ellen Magenis,K. Ikawa,Naoyuki Taniguchi,Charles J. Epstein +12 more
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TLDR
Except for a possible phenotypic contribution from the deletion of chromosome band 4q35, these data provide a molecular definition of the minimal region of chromosome 21 which, when duplicated, generates the facial features, heart defect, a component of the mental retardation, and probably several of the dermatoglyphic changes of DS.Abstract:
Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22. We now present evidence that significantly narrows the chromosomal region responsible for several of the phenotypic features of DS. We report a molecular and cytogenetic analysis of a three-generation family containing four individuals with clinical DS as manifested by the characteristic facial appearance, endocardial cushion defect, mental retardation, and probably dermatoglyphic changes. Autoradiograms of quantitative Southern blots of DNAs from two affected sisters, their carrier father, and a normal control were analyzed after hybridization with two to six unique DNA sequences regionally mapped on chromosome 21. These include cDNA probes for the genes for CuZn-superoxide dismutase (SOD1) mapping in 21q22.1 and for the amyloid precursor protein (APP) mapping in 21q11.2-21.05, in addition to six probes for single-copy sequences: D21S46 in 21q11.2-21.05, D21S47 and SF57 in 21q22.1-22.3, and D21S39, D21S42, and D21S43 in 21q22.3. All sequences located in 21q22.3 were present in three copies in the affected individuals, whereas those located proximal to this region were present in only two copies. In the carrier father, all DNA sequences were present in only two copies. Cytogenetic analysis of affected individuals employing R and G banding of prometaphase preparations combined with in situ hybridization revealed a translocation of the region from very distal 21q22.1 to 21qter to chromosome 4q. Except for a possible phenotypic contribution from the deletion of chromosome band 4q35, these data provide a molecular definition of the minimal region of chromosome 21 which, when duplicated, generates the facial features, heart defect, a component of the mental retardation, and probably several of the dermatoglyphic changes of DS. This region may include parts of bands 21q22.2 and 21q22.3, but it must exclude the genes S0D1 and APP and most of band 21q22.1, specifically the region defined by S0D1, SF57 and D21S47.read more
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Journal ArticleDOI
Down syndrome phenotypes: the consequences of chromosomal imbalance
Julie R. Korenberg,Xiao Ning Chen,R. Schipper,Z. Sun,R. Gonsky,S. Gerwehr,N. Carpenter,C. Daumer,P. Dignan,Christine M. Disteche +9 more
TL;DR: Evidence is provided for a significant contribution of genes outside the D21S55 region to the DS phenotypes, including the facies, microcephaly, short stature, hypotonia, abnormal dermatoglyphics, and mental retardation, which strongly suggests DS is a contiguous gene syndrome and augurs against a single DS chromosomal region responsible for most of the phenotypic features.
Journal ArticleDOI
Molecular mapping of twenty-four features of Down syndrome on chromosome 21.
Jean-Maurice Delabar,D. Théophile,Zohra Rahmani,Zoubida Chettouh,Jean-Louis Blouin,Marguerite Prieur,Bernard Noel,Pierre-Marie Sinet +7 more
TL;DR: The complex phenotype that constitutes Down syndrome may in large part simply result from the overdosage of only one or a few genes within the DCR and/or region D21S55-MX1.
Journal ArticleDOI
Hydrogen sulfide as a neuromodulator.
TL;DR: H2S is produced in response to neuronal excitation, and alters hippocampal long-term potentiation (LTP), a synaptic model for memory, and can also regulate the release of corticotropin-releasing hormone from hypothalamus.
Journal ArticleDOI
Genotype–phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21
Robert Lyle,Robert Lyle,Frédérique Béna,Frédérique Béna,Sarantis Gagos,Sarantis Gagos,Corinne Gehrig,Corinne Gehrig,Gipsy Lopez,Gipsy Lopez,Albert Schinzel,James Lespinasse,Armand Bottani,Armand Bottani,Sophie Dahoun,Sophie Dahoun,Laurence Taine,Martine Doco-Fenzy,Pascale Cornillet-Lefèbvre,Anna Pelet,Stanislas Lyonnet,Annick Toutain,Laurence Colleaux,Jürgen Horst,Ingo Kennerknecht,Nobuaki Wakamatsu,Maria Descartes,Judy Franklin,Lina Florentin-Arar,Sophia Kitsiou,Emilie Aït Yahya-Graison,Maher Costantine,Pierre-Marie Sinet,Jean M. Delabar,Stylianos E. Antonarakis,Stylianos E. Antonarakis +35 more
TL;DR: A BAC array spanning HSA21q and array comparative genome hybridization (aCGH) is developed and used to enable high-resolution mapping of pathogenic partial aneuploidies and unbalanced translocations involving HSA 21 to argue against a single DS critical region.
Journal ArticleDOI
Alzheimer's Disease in Down Syndrome: Neurobiology and Risk.
Warren B. Zigman,Ira T. Lott +1 more
TL;DR: The increase in lifespan for people with DS that has occurred over the past 100 years is described, as well as advances in the understanding of the occurrence of AD in adults with DS.
References
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Journal ArticleDOI
Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus
Rudolph E. Tanzi,James F. Gusella,Paul C. Watkins,G. A. P. Bruns,P. St. George-Hyslop,M L Van Keuren,D. Patterson,S. Pagan,David M. Kurnit,Rachael L. Neve +9 more
TL;DR: Overexpression of the gene in brain tissue from fetuses with Down syndrome (trisomy 21) can be explained by dosage since the locus encoding the beta protein maps to chromosome 21.
Journal ArticleDOI
Down's syndrome. The possibility of a pathogenetic segment on chromosome no. 21.
TL;DR: It is suggested, that trisomy of the band 21q22 might be pathogenetic in Down's syndrome and this paper contains a brief survey of 12 patients with a G/G translocation en tandem.
Journal ArticleDOI
Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome.
Charles J. Epstein,Karen B. Avraham,Michael Lovett,Sandra Smith,Orna Elroy-Stein,Galit Rotman,Cheryl G. Bry,Yoram Groner +7 more
TL;DR: These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes.
Journal ArticleDOI
Simultaneous fluorescent staining of R bands and specific heterochromatic regions (DA-DAPI bands) in human chromosomes
Journal ArticleDOI
Critical role of the D21S55 region on chromosome 21 in the pathogenesis of Down syndrome.
Zohra Rahmani,Jean-Louis Blouin,N Creau-Goldberg,P C Watkins,J F Mattei,M. Poissonnier,M Prieur,Zoubida Chettouh,A. Nicole,A Aurias +9 more
TL;DR: The size of the common duplicated region, localized on the proximal part of 21q22.3, is suspected to contain genes the overexpression of which is crucial in the pathogenesis of Down syndrome.
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