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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine which regions of chromosome 21 are involved in the pathogenesis of specific features of Down syndrome, we analysed, phenotypically and molecularly, 10 patients with partial trisomy 21. Six minimal regions for 24 features were defined by genotype-phenotype correlations. Nineteen of these features could be assigned to just 2 regions: short stature, joint hyperlaxity, hypotonia, major contribution to mental retardation and 9 anomalies of the face, hand and foot to the region D21S55, or Down syndrome chromosome region (DCR), located on q22.2 or very proximal q22.3, and spanning 0.4-3 Mb; 6 facial and dermatoglyphic anomalies to the region D21S55-MX1, including the DCR and spanning a maximum of 6 Mb on q22.2 and part of q22.3. Thus, 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.
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PMID:Molecular mapping of twenty-four features of Down syndrome on chromosome 21. 805 22

Mental retardation and dementia characteristic of Down's syndrome (DS) have a complex pathogenesis. Golgi and immunohistochemical studies were done on DS patients and controls from foetuses and elderly adults. Golgi studies on the cerebral cortex revealed that the postsynaptic spines on the basal dendrites increase from neonate to 15 years of age and gradually decrease after 20 years in controls, but poorly increase in children and rapidly decrease in adults with DS. This deficient synaptogenesis and dendritic atrophy may be related to mental retardation. On the other hand, immunohistochemistry on proteins, whose genes are located on chromosome 21, revealed that c-terminal protein of beta-amyloid appears in neurons of DS, S-100-positive glia increases in the hippocampus of neonates and adults, and membrane protein OK-2 is expressed earlier and is more widespread in the DS brains. The overexpression and early appearance of gene products in DS brains may be related to the pathogenesis of or predisposition to mental disorders or to dendritic hypogenesis.
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PMID:Dendritic and histochemical development and ageing in patients with Down's syndrome. 806 72

The triplication of a region of chromosome 21 around D21S55 in 21q22.2-22.3 has been involved in the main features of Down syndrome including mental retardation (Down syndrome chromosome region: DCR). To improve the physical map of this region, we screened yeast artificial chromosome (YAC) libraries with ETS2 and ERG sequences. Five selected clones were analyzed by AluPCR, pulsed-field gel electrophoresis, and in situ hybridization. A 1.2-Mg contig, encompassing the protooncogenes ETS2 and ERG, was identified, its restriction map established and compared to the genomic map. ERG is distal to D21S55 and proximal to ETS2. ERG and ETS2 genes are 400 kb apart and in opposite orientations. The contig contains the distal boundary and part of the DCR. Three putative HTF islands were identified.
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PMID:Mapping the Down syndrome chromosome region. Establishment of a YAC contig spanning 1.2 megabases. 806 51

Down syndrome (DS) is a major cause of mental retardation and congenital heart disease. Besides a characteristic set of facial and physical features, DS is associated with congenital anomalies of the gastrointestinal tract, an increased risk of leukemia, immune system defects, and an Alzheimer-like dementia. Moreover, DS is a model for the study of human aneuploidy. Although usually caused by the presence of an extra chromosome 21, subsets of the phenotypic features of DS may be caused by the duplication of small regions of the chromosome. The physical map of chromosome 21 allows the molecular definition of the regions duplicated in these rare cases of partial trisomy. As a first step in identifying the genes responsible for individual DS features and their pathophysiology, a panel of cell lines derived from 16 such individuals has been established and the molecular break points have been determined using fluorescence in situ hybridization and Southern blot dosage analysis of 32 markers unique to human chromosome 21. Combining this information with detailed clinical evaluations of these patients, we have now constructed a "phenotypic map" that includes 25 features and assigns regions of 2-20 megabases as likely to contain the genes responsible. This study provides evidence 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. This strongly suggests DS is a contiguous gene syndrome and augurs against a single DS chromosomal region responsible for most of the DS phenotypic features.
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PMID:Down syndrome phenotypes: the consequences of chromosomal imbalance. 819 71

The phenotype of the brain in Down syndrome is different from that of a normal child both in its reduced size and altered gyral configuration. Underlying the mental retardation are neuronal abnormalities, including alterations of cortical lamination, reduced dendritic ramifications, and diminished synaptic formation. However, cholinergic enzymes such as choline acetyl transferase and acetyl cholinesterase have shown no abnormalities in young children with Down syndrome. The pace of dendritic maturation is altered in Down syndrome. In infancy, the normal dendritic tree continuously expands; in Down syndrome, at 4 months of age, the neurons show a relatively expanded tree, but during the first year, the dendrites stop growing and become atrophic relative to control neurons. To relate these phenotypic alterations to chromosome 21, we examined the gene products of several genes localized to chromosome 21. Identification of such genes and determination of their gene product allow the production of specific antibodies and the identification, through immunohistochemical techniques, of the expression of these proteins in both normal development and Down syndrome. Specifically, the localization and appearance during development of proteins such as S100 beta, beta A4-amyloid, superoxide dismutase, and OK-2 are providing links between genotype and phenotype. S100 beta protein is of particular interest because of its effect in vitro on neuritic outgrowth and its increased expression in the temporal lobe in Down syndrome. The brains of transgenic mice bearing multiple copies of the human S100 gene show some comparable changes to those in Down syndrome. These experimental approaches provide the means for better understanding the cellular and molecular basis for the mental retardation in Down syndrome.
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PMID:Association of phenotypic abnormalities of Down syndrome with an imbalance of genes on chromosome 21. 831 92

Down syndrome (DS) (trisomy 21) is the most frequent genetic cause of mental retardation in man. The gene coding for the beta subunit of human S100 protein (S100 beta) has been mapped to chromosome 21. The dimeric form of S100 beta may function as a neurotrophic factor in the CNS and may also influence the establishment of hippocampal long-term potentiation (LTP). To study the behavioral consequences of overexpression of S100 beta in an animal model, we derived four lines of transgenic mice carrying multiple copies of the human S100 beta gene. The human S100 beta gene was expressed in the brain of these mice in a cell-specific and gene-dose-dependent manner. The motor and posture patterns of 16-month-old transgenic mice and their control (non-transgenic) littermates were studied in two tests, open field and bar-crossing, in order to examine novelty induced exploratory activities. Transgenic female mice were significantly hyperactive in both tests in comparison with their female control littermates. These differences were independent of the line of origin of the mice suggesting a causal relationship between the observed hyperactivity and the presence of multiple copies of the integrated human S100 beta gene. In contrast, transgenic males were not hyperactive in comparison with controls. Neither male nor female transgenic mice displayed any coordination defects. We speculate about how an interaction between the effects of elevated S100 beta levels and female specific hormonal changes could have resulted in the observed female restricted hyperactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Female transgenic mice carrying multiple copies of the human gene for S100 beta are hyperactive. 832 26

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. These rare cases define a minimal region for the Down syndrome phenotype encompassing about 3 Mb around D21S55. By using a new method for the identification of coding sequences (Alu-splice PCR) we have identified a new gene, DSCR1, from region 21q22.1-q22.2. DSCR1 encodes a novel protein which has an acidic domain, a serine-proline motif, a putative DNA binding domain and a proline-rich region with the characteristics of a SH3 domain ligand. These features suggest that DSCR1 could be involved in transcriptional regulation and/or signal transduction. DSCR1 is highly expressed in human brain and heart, and increased expression in the brains of young rats compared with adults suggests a role for DSCR1 during central nervous system development. Structural characteristics, together with its particular expression in brain and heart, encourage us to suggest that the overexpression of DSCR1 may be involved in the pathogenesis of Down syndrome, in particular mental retardation and/or cardiac defects.
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PMID:A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart. 859 18

The Down syndrome (DS) region on chromosome 21, which is responsible for the main features of DS such as characteristic facial features, a congenital heart defect, and mental retardation, has been defined by molecular analysis of DS patients with partial trisomy 21. The 2. 5-Mb region around the marker D21S55 between D21S17 and ERG in 21q22 is thought to be important, although contributions of other regions cannot be excluded. In this region, we focused on a 1.6-Mb region between a NotI site, LA68 (D21S396, which is mapped distal to D21S17) and ERG, because analysis of a Japanese DS family with partial trisomy 21 revealed that the proximal border of its triplicated region was distal to LA68. We constructed P1 contigs with 46 P1 clones covering more than 95% of the 1.6-Mb region. A high-resolution restriction map using BamHI was also constructed for more detailed analysis. Our P1 contig map supplements other physical maps previously reported and provides useful materials for further analysis including gene isolation and sequencing of the DS region.
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PMID:A 1.6-Mb P1-based physical map of the Down syndrome region on chromosome 21. 861 11

We report on the clinical and cytogenetic assessment of five cases of Down syndrome phenotype with either a partial duplication of chromosome 21 or a normal karyotype, and we quote a case of del (21q) syndrome. Down syndromes with a partial duplication of chromosome 21 (as well as cases of del (21q), which are partly the phenotypic countertype of trisomy 21) are of paramount importance in the understanding of genes involved in the phenotype of Down syndrome. The goal is to find the relevant genes implicated in the main traits of Down syndrome (i.e. mental retardation, Alzheimer disease, and serious visceral malformations). Such a goal, in our opinion, cannot be reached just by publishing the genotype and the phenotype of a small cohort of patients: 1. a sufficient number of accurate cases is needed, and 2. data have to be computerized for definite conclusions to be reached. The main aims of this report are to present our study protocol and to invite colleagues to participate in a collaborative study in order to collect a maximum of these (rare) cases.
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PMID:Down syndrome with partial duplication and del (21) syndrome: study protocol and call for collaboration. Study I: Clinical assessment. 872 67

Trisomy 21 is the most common aneuploidy in humans with a frequency of 1 in 700 live births and is by far the most common defined cause of mental retardation. To analyse which of the chromosome 21 genes is overexpressed early in development-giving rise to the Down syndrome phenotype-and to provide candidate genes for other HSA21 disease loci, we need a transcription map of the chromosome. Therefore, to enrich the gene map of human chromosome 21 we have undertaken a systematic approach to fine mapping and characterising expressed sequences generated by the various cDNA sequencing projects. In this report we show the localisation of the CAF1P60 gene to human chromosome 21 and its fine mapping to 21q22.2 between D21S333 and D21S334. This mapping position places CAF1P60 in a region of HSA21 which is strongly associated with the major features of Down syndrome. The function of this gene product may have important implications for the phenotype that arises from trisomy 21.
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PMID:The gene encoding the p60 subunit of chromatin assembly factor I (CAF1P60) maps to human chromosome 21q22.2, a region associated with some of the major features of Down syndrome. 879 29


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