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

Chromosome imbalance (aneusomy) is the leading known cause of both spontaneous abortion and mental retardation in human beings. The primary abnormality is thought to result from quantitative changes of transcription products from the unbalanced genetic material. To document this point, I compared chromosome 21-specific transcription in skin fibroblasts from subjects with monosomy 21, disomy 21 (normal), and trisomy 21 (Down syndrome). Polyadenylylated RNA [poly(A)-RNA], which is enriched in messenger and messenger-precursor RNA sequences, was isolated from the above fibroblast lines. Radioactive DNA (cDNA) complementary to these RNAs was synthesized with reverse transcriptase (RNA-dependent DNA polymerase). These cDNAs were hybridized with (i) DNA from a cell line with a mouse genome plus human chromosome 21 and (ii) mouse DNA. Subtraction of the amount of hybridization in experiment ii from that in experiment i yielded a measure of human chromosome 21-specific RNA sequences. The results were consistent with gene dosage at the transcriptional level; for monosomy 21-derived cDNA, 0.6% (of the total cDNA) hybridized specifically to human chromosome 21; for disomy 21-derived cDNA, 2% hybridized; and for trisomy 21-derived cDNA, 3% hybridized. Thus, for DNA sequences on chromosome 21 in human skin fibroblasts, transcription depends on DNA dosage. Characterization of the chromosome 21-specific RNA sequences quantitated in these experiments could help to elucidate the mechanisms by which abnormal karyotypes result in abnormal phenotypes.
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PMID:Down syndrome: gene dosage at the transcriptional level in skin fibroblasts. 15 66

Three Down syndrome patients for whom karyotypic analysis showed a "mirror" (reverse tandem) duplication of chromosome 21 were studied by phenotypic, cytogenetic, and molecular methods. On high-resolution R-banding analysis performed in two cases, the size of the fusion 21q22.3 band was apparently less than twice the size of the normal 21q22.3, suggesting a partial deletion of distal 21q. The evaluation of eight chromosome 21 single-copy sequences of the 21q22 region--namely, SOD1, D21S15, D21S42, CRYA1, PFKL, CD18, COL6A1, and S100B--by a slot blot method showed in all three cases a partial deletion of 21q22.3 and partial monosomy. The translocation breakpoints were different in each patient, and in two cases the rearranged chromosome was found to be asymmetrical. The molecular definition of the monosomy 21 in each patient was, respectively, COL6A1-S100B, CD18-S100B, and PFKL-S100B. DNA polymorphism analysis indicated in all cases a homozygosity of the duplicated material. The duplicated region was maternal in two patients and paternal in one patient. These data suggest that the reverse tandem chromosomes did not result from a telomeric fusion between chromosomes 21 but from a translocation between sister chromatids. The phenotypes of these patients did not differ significantly from that of individuals with full trisomy 21, except in one case with large ears with an unfolded helix. The fact that monosomy of distal 21q22.3 in these patients resulted in a phenotype very similar to Down syndrome suggests that the duplication of the genes located in this part of chromosome 21 is not necessary for the pathogenesis of the Down syndrome features observed in these patients, including most of the facial and hand features, muscular hypotonia, cardiopathy of the Fallot tetralogy type, and part of the mental retardation.
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PMID:No significant effect of monosomy for distal 21q22.3 on the Down syndrome phenotype in "mirror" duplications of chromosome 21. 146 8

A 9-year-old boy was referred for evaluation of multiple anomalies and mental retardation. Skeletal abnormalities had been noted at birth: joint contractures, right acetabular "dysplasia," ulno-fibular dysostosis, and bilateral talipes equinovarus with calcaneocuboid fusion. Additional findings at 9 years included short stature, unusual facial appearance, camptodactyly of several digits, undescended testes, and syndactyly of toes 4 and 5. On psychological testing he was found to be moderately retarded. Cytogenetic analysis of chromosome bands using Q, GTG, R, and C banding showed an interstitial deletion of 21q; karyotype designation: 46,XY, del (21)(pter----q11.2::q22.1----qter). Parental chromosomes were normal. Manifestations in this boy, including the joint contractures, are similar to those described in the monosomy 21 syndrome. Ulno-fibular dysostosis has not been reported previously with abnormalities of chromosome 21. To our knowledge, this is the second patient reported with an interstitial deletion of chromosome 21, and the patients are phenotypically dissimilar.
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PMID:De novo 21q interstitial deletion in a retarded boy with ulno-fibular dysostosis. 397 70

We compared the phenotypes, karyotypes, and molecular data for six cases of partial monosomy 21. Regions of chromosome 21, the deletion of which corresponds to particular features of monosomy 21, were thereby defined. Five such regions were identified for 21 features. Ten of the features could be assigned to the region flanked by genes APP and SOD1: six facial features, transverse palmar crease, arthrogryposis-like symptoms, hypertonia, and contribution to mental retardation. This region, covering the interface of bands 21q21-21q22.1, is 4.7-6.4 Mb long and contains the gene encoding the glutamate receptor subunit GluR5 (GRIK1).
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PMID:Molecular mapping of 21 features associated with partial monosomy 21: involvement of the APP-SOD1 region. 910 47

Ring chromosome 21 is a rare chromosome anomaly often associated with mental retardation and dysmorphic features. Less commonly, the ring chromosome can be familial and associated with a normal phenotype. Phenotypically normal female carriers, however, are at increased risk of having children with Down syndrome, mosaic monosomy 21, and variable duplication or deletion of chromosome 21. Because of the relative mitotic and meiotic instability of ring chromosomes, abnormal cytogenetic findings encountered during prenatal diagnosis may not reflect the true genetic status of the fetus. This is a report of a phenotypically normal female carrier of a familial ring 21 chromosome. Prenatal diagnosis on her twin pregnancy revealed a mosaic 46,XX,r(21)(p13;q22) (77 per cent)/45,XX,-21 in one fetus and a normal male karyotype in the second. The pregnancy was carried to term. Both infants are completely normal, with a non-mosaic ring 21 karyotype from the lymphocytes of one twin. The diagnostic uncertainty and problematic genetic counselling related to fetal cytogenetic abnormalities are the subjects of this report.
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PMID:Prenatal diagnosis of familial ring 21 chromosome. 778 85

The gene encoding the dual-specificity tyrosine-regulated kinase DYRK1A maps to the chromosomal segment HSA21q22.2, which lies within the Down syndrome critical region. The reduction in brain size and behavioral defects observed in mice lacking one copy of the murine homologue Dyrk1A (Dyrk1A+/-) support the idea that this kinase may be involved in monosomy 21 associated mental retardation. However, the structural basis of these behavioral defects remains unclear. In the present work, we have analyzed the microstructure of cortical circuitry in the Dyrk1A+/- mouse and control littermates by intracellular injection of Lucifer Yellow in fixed cortical tissue. We found that labeled pyramidal cells were considerably smaller, less branched and less spinous in the cortex of Dyrk1A+/- mice than in control littermates. These results suggest that Dyrk1A influences the size and complexity of pyramidal cells, and thus their capability to integrate information.
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PMID:Alterations in the phenotype of neocortical pyramidal cells in the Dyrk1A+/- mouse. 1613 72

Fragile X syndrome (FXS) is a well-recognized mental retardation syndrome with characteristic facial features and behavioural phenotype. Monosomy 21 is a rare cytogenetic aberration for which clinical features were incompletely defined since full monosomy 21 is incompatible with life. A 5-year-old male patient with FXS and low-grade mosaicism for full monosomy 21 (46,XY[96%]/45,XY,-21[4%]) is presented. He had lack of speech and severely impaired social skills, hyperactivity, stereotypical hand movements, a special interest towards moving colourful items and a short attention span for other objects around. He had macrocephaly, a rather long face, prominent occiput and prominent midface, retrognathia, down-slanting palpebral fissures, hypertelorism and cup-shaped, posteriorly rotated and low-set ears. Full monosomy in the aberrant cell line was proven by whole chromosome painting. FXS was previously reported to accompany sex chromosome aneuploidies; however, to the best of our knowledge, the present patient is the first FXS patient with an aberration involving autosomes. He contributes to the current knowledge on monosomy 21 phenotype, having dysmorphic facial findings despite the concurrent phenotypic expression of the FXS. As a last conclusion, cytogenetic analysis must be done to all mentally retarded patients with minor dysmorphic features.
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PMID:Coexistent mosaic monosomy 21 and fragile X syndrome in a mentally retarded male patient. 1771 Aug 69

Down syndrome (DS) is one of the most frequent congenital birth defects, and the most common genetic cause of mental retardation. In most cases, DS results from the presence of an extra copy of chromosome 21. DS has a complex phenotype, and a major goal of DS research is to identify genotype-phenotype correlations. Cases of partial trisomy 21 and other HSA21 rearrangements associated with DS features could identify genomic regions associated with specific phenotypes. We have developed a BAC array spanning HSA21q and used array comparative genome hybridization (aCGH) to enable high-resolution mapping of pathogenic partial aneuploidies and unbalanced translocations involving HSA21. We report the identification and mapping of 30 pathogenic chromosomal aberrations of HSA21 consisting of 19 partial trisomies and 11 partial monosomies for different segments of HSA21. The breakpoints have been mapped to within approximately 85 kb. The majority of the breakpoints (26 of 30) for the partial aneuploidies map within a 10-Mb region. Our data argue against a single DS critical region. We identify susceptibility regions for 25 phenotypes for DS and 27 regions for monosomy 21. However, most of these regions are still broad, and more cases are needed to narrow down the phenotypic maps to a reasonable number of candidate genomic elements per phenotype.
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PMID:Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21. 1900 11

Copy-number variation in the human genome can be disease-causing or phenotypically neutral. This type of genetic rearrangement associated with human chromosome 21 (Hsa21) underlies partial Monosomy 21 and Trisomy 21. Mental retardation is a major clinical manifestation of partial Monosomy 21. To model this human chromosomal deletion disorder, we have generated novel mouse mutants carrying heterozygous deletions of the 2.3- and 1.1-Mb segments on mouse chromosome 10 (Mmu10) and Mmu17, respectively, which are orthologous to the regions on human 21q22.3, using Cre/loxP-mediated chromosome engineering. Alterations of the transcriptional levels of genes within the deleted intervals reflect gene-dosage effects in the mutant mice. The analysis of cognitive behaviors shows that the mutant mice carrying the deletion on either Mmu10 or Mmu17 are impaired in learning and memory. Therefore, these mutants represent mouse models for Monosomy 21-associated mental retardation, which can serve as a powerful tool to study the molecular mechanism underlying the clinical phenotype and should facilitate efforts to identify the haploinsufficient causative genes.
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PMID:Deficiencies in the region syntenic to human 21q22.3 cause cognitive deficits in mice. 2051 40