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

In trisomy 21, pathogenesis of mental retardation is still poorly understood although the knowledge of the genic content of chromosome 21 is steadily increasing. Short of discovering how to silence selectively one of the 3 chromosomes 21, no rational medication can be envisaged before pathogenesis has been unraveled, at least partially. A biochemical scheme of impairment of mental efficiency is presented. Secondarily, the possible deleterious effects of a given gene overdose are discussed. Cu/Zn SOD, cystathionine beta synthase, S 100 beta protein, phosphofructokinase, purine synthesis and adenosine pharmacology, thyroid disturbance, and elevated TSH with low rT3 as well as biopterine metabolism interferences are reviewed. It is observed that the metabolic paths controlled by these genes, although unrelated at first glance, are in fact tightly related by their effects, just as if synteny was in some way related to biochemical cooperation or mutually controlled regulation. Experiments in vitro have demonstrated a peculiar sensitivity of trisomic 21 lymphocytes to methotrexate. From this starting point, systematic research of special sensitivities has begun. Clinical observations and relevant statistical methods allow study of the speed of mental development under various medications. The interest of regulating thyroid metabolism, when needed, is exemplified. Reequilibration of monocarbon metabolism is discussed and the seemingly favourable effect of folinic acid medication in pseudo-Alzheimer complication is presented.
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PMID:Pathogenesis of mental deficiency in trisomy 21. 214 47

Review of the clinical cytogenetic literature provides compelling evidence for a specific relationship between imbalance of particular chromosomes or chromosomal regions and the appearance of defined patterns of phenotypic abnormalities. In many instances, detailed phenotypic mapping has made it possible to assign portions of a phenotype to relatively small chromosome segments, which are sometimes referred to as "critical regions." However, since these regions are usually defined by a subset of the phenotypic manifestations of an aneuploidy syndrome--generally those anomalies that are regarded as most characteristic or readily observable--it is important not to fall into the trap of thinking that it is imbalance of only these regions that has deleterious effects on development and function. Thus, in Down syndrome, the presence of an extra copy of the proximal part of 21q22.3 appears to result in the typical physical phenotype--as defined principally in terms of the characteristic facial and hand anomalies and congenital heart defect--in addition to mental retardation. But, duplication of proximal 21q also affects mental development, and the regions responsible for many other aspects of the Down syndrome phenotype, including Alzheimer disease, have not been defined at all. Therefore, it remains likely that loci present on many parts of the long arm of chromosome 21 play a role in the development of the overall phenotype of Down syndrome. The immediate effect at the molecular level of an aneuploidy-caused alteration in gene dose appears to be a non-compensated commensurate change in the production of gene products.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The consequences of chromosome imbalance. 214 68

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 q22. Molecular and cytogenetic analysis of a family with 4 DS members has significantly narrowed the chromosomal region responsible for the DS phenotype: congenital heart disease, facial features, and possibly dermatoglyphics. Using high-resolution chromosome banding and in situ hybridization, we found the DS phenotype in the family is caused by a duplication of chromosome 21 material including a region of distal band q22.1 below the limit of cytogenetic resolution, in addition to bands q22.2-q22.3. By quantitative Southern blot analyses of DS members of the family, all random DNA sequences and expressed genes mapping in band q22.1 and proximal are found not to be duplicated. These include cDNA probes for the genes for superoxide dismutase (SOD1) mapping in 21q22.1 and for the amyloid precursor protein (APP) mapping in 21q21.05; D21S46 in 21q11.2-21.05; and D21S47 and SF57 in 21q22.1-q22.3. With one exception, DNA sequences mapping in band q22.3 are duplicated (D21S39, D21SD42, and D21S43). This analysis has now been extended to show that D21S17, previously mapped to band 21q22.3, is not duplicated. In conclusion, the genes SOD1 and APP have been excluded from a necessary role in generating the classical DS features, and the proximal border of the chromosomal region causing DS has been defined.
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PMID:Down syndrome: toward a molecular definition of the phenotype. 214 83

We report on a family with transmission of a ring chromosome 14 from an affected mother to her 2 sons. The mother was mosaic, 46,XX,r(14)/45,XX,t(14q21q). Both of her sons, affected by seizures and mental retardation, have the karyotype 46,XY,r(14). In considering the association of translocation 14:21 in the mother with ring 14, we postulate that either the ring chromosome was formed first and then opened with translocation of the partially deleted chromosome 14 to chromosome 21, or the 14:21 translocation was present first, then the chromosomes 14 and 21 broke apart, and the partially deleted 14 formed the ring. The published literature of cases of ring 14 is reviewed.
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PMID:Transmission of ring 14 chromosome from mother to two sons. 220 11

Analysis of partial duplication of chromosome 21 suggests that band 21q22 contains determinants for the Down syndrome. We report two cases of free proximal trisomy 21 without manifestations of the Down syndrome. Phenotypic anomalies included marked microcephaly, short stature, hypoplastic nails, and mental retardation/developmental delay. Our cases are consistent with the assignment of band 21q22 as the causal duplicated segment in the Down syndrome.
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PMID:Free proximal trisomy 21 without the Down syndrome. 244 9

Trisomy 21 (Down's syndrome, DS) is the most frequent chromosomal aberration. Triplication of a small region of chromosome 21, the fragment 21q22 is sufficient to cause the DS phenotype including immunodeficiency, premature aging, neurodegenerations, mental retardation and an increased risk of leukemia. Chromosomal aberrations caused by X-ray irradiation were observed in DS lymphocytes and DS fibroblasts, but the correlation to cell death or repair deficiency was not clear. We approached this problem and report here on a profound X-ray repair deficiency of DS cells. With a colorimetric viability assay we observed an UV sensitivity of DS fibroblasts at doses beyond 14 Jm-2 but no significant X-ray sensitivity. By the nucleoid sedimentation technique, a deficient restoration of nucleoids in DS cells after X-ray irradiation was demonstrated. The same features apply for cells, which contain an overexpressed Cu/Zn-superoxide dismutase (SOD-1) gene. Radiation sensitivity of DS cells and SOD-1 overexpressing cells resemble those of ataxia telangiectasia (AT) fibroblasts. Additionally, DS and AT cells exert lack of inhibition of DNA synthesis after X-ray irradiation.
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PMID:Radiation sensitivity of Down's syndrome fibroblasts might be due to overexpressed Cu/Zn-superoxide dismutase (EC 1.15.1.1). 252 18

Trisomy of the whole or distal part of human chromosome 21 (HSA 21) (Ts21) results in Down Syndrome (DS), which is characterized in part by mental retardation and associated neurological abnormalities. Structural abnormalities observed frequently include reduced brain weight, decreased number and depth of sulci in the cerebral cortices, neuronal heterotopias, and reduced numbers of specific populations of neurons, such as granule cells, in the cerebral cortices. Abnormalities in the structure of cells, primarily of the dendrites, are observed in portions of the neuraxis, such as the hippocampus, cerebellum, and cerebral cortices. Functional abnormalities in membrane properties in peripheral structures and in neurotransmitter enzyme systems in both peripheral and central structures are observed also. Brains of DS individuals over the age of 40 exhibit the characteristic neuropathologic and neurochemical stigmata of Alzheimer's disease (AD). The cholinergic and noradrenergic systems appear to be particularly vulnerable. To elucidate the mechanisms responsible for these abnormalities, identification of the genes located in the distal part of HSA 21 and the systematic study of animal model systems with close genetic homology are essential.
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PMID:The neurobiologic consequences of Down syndrome. 287 70

Between 1974 and 1987, 232 translocation carriers have been detected in our Center; they belong to 144 different families. Indications for chromosome analysis were the following: familial studies in relation with a patient suggesting a chromosome anomaly (25.4%); mental retardation with or without malformations (24.6%); 2 or more spontaneous abortions (17.2%); infertility problems, mainly male (16.4%); genetic counseling for a non-chromosomal disease (9.5%); prenatal diagnosis in risk pregnancies (6.9%). The chromosome anomalies detected were the following; balanced Robertsonian fusions (114 cases = 49.1%); balanced translocations (74 cases = 31.9%); unbalanced translocations, Robertsonian fusions included (44 cases = 19%). Two groups may be distinguished: the first one confirms data already known, such as high frequency of balanced translocations in couples with multiple abortions, or in infertile males. The second group on the contrary shows more unusual observations: 4 cases of standard trisomy 21 born to young parents carriers of a balanced translocation not involving chromosome 21; 5 cases of trisomy 13 with 46 chromosomes and a Robertsonian fusion, born to parents carriers of a t(13q; Dq) (twice the mother and thrice the father); 14 cases of apparently balanced translocations, however with an abnormal phenotype; and finally 22 cases of balanced translocations incidentally detected during the course of investigations in patients with a genetic problem generally not associated with a chromosome defect.
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PMID:[Chromosome translocations: study of 232 cases originating from 144 families]. 296 87

Autosomal aneuploidy in mammals adversely affects developmental processes. In human beings, for example, trisomy 21 is the most frequent aneuploidy detected among newborns and the most common known genetic cause of mental retardation. In this review, several hypotheses are discussed that have been proposed to explain the mechanisms by which aneuploidy (especially trisomy) disrupts development. These mechanisms included specific gene dosage effects, generalized disruption of genetic homeostasis, and the influence of the parental origin of the duplicated chromosome. The availability of specific chromosomal rearrangements in mice, coupled with selective breeding schemes, permits generation of aneuploidy of specific chromosomes or chromosomal segments on controlled genetic backgrounds, thus enabling the systematic study of the causes and consequences of defined aneuploidy. Phenotypic characteristics associated with a number of specific aneuploidies in the mouse are discussed. Emphasis is placed on the effects of trisomy 16. Genetic homology between mouse chromosome 16 and human chromosome 21 has led investigators to suggest that analogous mechanisms will be responsible for the developmental abnormalities produced in these respective aneuploidies. Analysis of trisomy 16 mice from the organismal to the subcellular level has revealed a number of phenotypic characteristics (particularly neurobiologic ones) shared with human trisomy 21. The dosage effects of shared genes (or their products) may contribute to the development of these features.
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PMID:Developmental consequences of autosomal aneuploidy in mammals. 297 93

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


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