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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of neurodevelopmental disorders are caused by defects in activity dependent neuronal plasticity, the process by which neuronal activity shapes developing neuronal circuits. These disorders are caused by genetic mutations or other factors that disrupt intracellular signaling pathways that link the cell surface with the nuclear machinery for gene expression. The signaling pathways disrupted by these disorders are involved in learning, memory and behavior as well as in the synaptic proliferation and pruning that occurs during normal development. Examples of neurodevelopmental disorders that target plasticity include X-linked disorders such as Rett, Fragile-X and Coffin-Lowry Syndromes as well as acquired disorders such as cretinism. Several other X-linked mental retardation syndromes as well as autosomal disorders including neurofibromatosis type 1 and tuberous sclerosis also involve signaling pathways involved in neuronal plasticity. Disruption of neuronal plasticity is a mechanism that may underlie a diverse group of neurodevelopmental disorders.
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PMID:Developmental disorders of activity dependent neuronal plasticity. 1140 58

Methylation of genomic CpG residues is crucial for proper neuronal function. Rett syndrome, a common form of mental retardation, is associated with mutations in the gene encoding MeCP2, a methyl CpG binding protein linked to transcriptional repression. Gene knockouts of mouse Mecp2 have reproduced key aspects of the disease. A CNS-restricted knockout of Dnmt1, encoding the enzyme that maintains CpG methylation patterns, results in loss of mutant neurons and glia.
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PMID:Methylated cytosine and the brain: a new base for neuroscience. 1143 Jul 98

Molecular cytogenetic and cytogenetic studies of chromosomal disorders in patients with nervous and mental disorders were conducted using currently available approaches, including fluorescence in situ hybridization (FISH) with an original collection of centromeric, telomeric, region-specific DNA probes. A novel in situ hybridization protocol for rapid (15-30 min) chromosomal detection procedure and directly fluoresceinated DNA probes are recommended for use in mental retardation and congenital malformations. Chromosomal abnormalities could be detected in postnatal cases with chromosomal structural rearrangements, aneuplodies of gonosomes (including mosaicisms) and autosomes (including marker chromosomes). Molecular cytogenetics (or FISH diagnosis) can be used when classical cytogenetic methods are insufficient. The authors' experience shows that FISH should be utilized only as an adjunctive test for classical cytogenetic studies when banding techniques are ineffective; cytogenetic methods should be utilized for the preclinical diagnosis of Rett's syndrome. Detection by original probes gives an additional possibility in FISH analysis. Molecular cytogenetic methods are shown to provide a rapid accurate approach to studying and diagnosing chromosomal anomalies and disorders in mental retardation with congenital malformations and Rett's syndrome in children and to exploring aneuploidies in the postmortem cell samples from schizophrenic patients.
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PMID:[Molecular cytogenetic studies of chromosomal abnormalities and disorders in nervous and mental diseases: search for biological markers for diagnosis]. 1152 24

The paper provides clinical and catamnestic descriptions of 240 children with infantile autism; 160 with atypical autism (of them 100 had schizophrenic attacks, 60 presented with mental retardation concurrent with atypical autism (in phenylketonuria, tuberose sclerosis, Down syndrome, Martin-Bell syndrome), 20 with Asperger's syndrome, 60 with Rett's syndrome, 20 with psychogenic paraautism according the Nissen classification. The similarity of autism-like disorders and atypical autism was considered. Syndromal verifications in accordance with ICD-10 (1994) and ICD-10 (1999) in Russian versions and clinical nosological verifications adopted in Russia were studied in all the examinees. New approaches to treating patients with autistic disorders were developed.
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PMID:[Current approaches to the problem of autism in childhood]. 1152 31

The search for targets of FMRP (the product of FMR1, the mutated gene in Fragile X syndrome) has predominantly focused on identifying transcripts that are regulated by this RNA-binding protein. This study introduces the use of two-dimensional gel electrophoresis (2D PAGE) as a novel approach for demonstrating changes in protein synthesis secondary to FMRP deficit. By a standardized 2D PAGE protocol, we studied leukocyte homogenates from 30 males with different patterns of FMR1 mutation and different levels of FMRP. Samples from these subjects were compared to those of 12 normal control males and eight subjects with other mental retardation-associated conditions (i.e., Rett and Down syndromes). We found an abnormal pattern of a major leukocytic protein, identified by 2D PAGE datasets and immunoblotting as annexin-1 (Anx-1). Anx-1 appeared in subjects with Fragile X as multiple rather than 1-2 spots, at approximately 37 kd, in the pI 5-7 range. The presence and intensity of this Anx-1 pattern was relatively independent of Anx-1 levels and inversely related to total and high MW FMRP immunoreactivities. Based on the 2D PAGE pattern, without obvious MW change, and on dephosphorylation assays, we concluded that Anx-1's abnormality represents an aberrant posttranslational modification other than phosphorylation. Comparisons of our data with published cytoskeletal protein 2D profiles suggest that Anx-1 may be abnormally acetylated and, consequently, incapable of establishing appropriate N-terminal protein-protein interactions. In addition to its peripheral anti-inflammatory function, Anx-1 mediates glucocorticoid inhibition of the hypothalamo-pituitary-adrenal axis. As the latter seems to be disrupted in Fragile X syndrome, the reported Anx-1 abnormality could be responsible for some aspects of the Fragile X neurobehavioral phenotype. Our data also emphasize the feasibility of using 2D PAGE for disclosing molecular abnormalities in Fragile X and other genetic disorders.
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PMID:Annexin-1 is abnormally expressed in fragile X syndrome: two-dimensional electrophoresis study in lymphocytes. 1156 39

Dysfunction of the prefrontal cortex may contribute to the autistic features and mental retardation of Rett syndrome, a neuropsychiatric condition caused by mutations of the gene encoding methyl-CpG-binding protein 2 (MeCP2). Because nothing is known about the expression of MeCP2 and other chromatin-associated factors in primate brain, we studied in monkey prefrontal cortex and murine cerebral cortex expression patterns of MeCP2 and of macrohistone H2A (MacroH2A), which like MeCP2 is associated with transcriptionally silent chromatin. In both species, MeCP2 and MacroH2A appeared to be ubiquitously expressed by cortical neurons, including projection neurons and GABAergic interneurons. In the adult monkey, MeCP2 expression was robust throughout all layers of the prefrontal cortex but it was limited in fetal monkeys at embryonic day 110 to the deeper cortical layers and the subplate. These results suggest that MeCP2 may be important for neuronal maintenance in the developing and in the mature primate prefrontal cortex, consistent with the previously reported phenotype of MeCP2-null mutant mice.
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PMID:Expression pattern of the Rett syndrome gene MeCP2 in primate prefrontal cortex. 1159 48

Recent studies have demonstrated that biogenic amines have a function of facilitating formation and maintenance of synapses in diverse regions of the central nervous system in developing and adult animals. The normal number of synapses maintained by biogenic amines are crucial to acquire learning and memory. The level of biogenic amines was reported to decrease in the brain by several neurodevelopmental disorders associated with mental retardation and developmental disabilities such as Rett syndrome, autism and Down syndrome. Taken into consideration this fact together with the function of biogenic amines for synapses, the density of synapses appears to decrease considerably in the brains of patients suffered from the neurodevelopmental disorders. The synaptic overproduction during the critical period of development especially 1 year after birth has been considered as a background mechanism to provide plasticity for the developing brain. Synaptic overproduction does not appear to occur in the brains of patients suffered from the neurodevelopmental disorders, which they are observed mental retardation occurring in the first 1 year after birth. Along with the neurodevelopmental disorders, environmental factors (stress, drugs and nutrition) during pre- and post-natal critical developmental periods are known to change levels of biogenic amines in the brain. In fact, maternal stress has been shown to decrease the levels of serotonin and the density of synapses in the hippocampus of the offspring, and they showed developmental disabilities in the spatial learning and memory. A cascade appears to exist from either the child neurological disorders or the environmental factors to mental retardation and developmental disabilities by decreases in the levels of biogenic amines and synaptic density.
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PMID:A biogenic amine-synapse mechanism for mental retardation and developmental disabilities. 1173 35

Rett syndrome, an X-linked neurodevelopmental disorder, is a major cause of mental retardation in females. Recent genetic analyses have revealed that mutations in the methyl-CpG-binding protein gene encoding MeCP2 are associated with Rett syndrome. In this study, we used transient expression systems to investigate the functional significance of mutations seen in patients with Rett syndrome. Missense mutations in the methyl-CpG-binding domain were analyzed by the transfection in mouse L929 cells and Drosophila SL2 cells. The L929 cells were utilized to investigate the effects of mutations on the affinity for heterochromatin, where methylated CpG dinucleotides are extremely enriched. The SL2 cells were utilized to analyze their effects on transcriptional repression activities. R106W and F155S mutations led to the substantial impairment of MeCP2 functions, showing the loss of accumulation of the mutated protein to mouse heterochromatin and the reduction of the transcriptional repressive activity in Drosophila SL2 cells. Intriguingly, the R133C mutant retained the functionality equivalent to MeCP2 in these analyses. On the other hand, the T158M mutation exhibited the intermediate level of the impairment of functions in both analyses. Thus, these functional assays are useful to evaluate the consequences of mutation in the methyl-CpG-binding domain of MeCP2 and provide an insight into the relationship between the genotype and the severity of Rett syndrome.
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PMID:Functional analyses of MeCP2 mutations associated with Rett syndrome using transient expression systems. 1173 66

Rett syndrome is a neurodevelopmental disorder characterized by cognitive and adaptive regression with autistic features, loss of acquired skills, and stereotypic hand movements that almost exclusively affects females. It is an X-linked dominant disorder, with presumed lethality in males. Nonetheless, there are a few descriptions of males suspected of having Rett syndrome. With the recent discovery that the MECP2 gene is responsible for most cases of Rett syndrome, it is possible to molecularly assess cases of affected males by direct sequencing analysis. We describe an Israeli family consisting of a female having classic Rett syndrome and a male sibling with severe neonatal encephalopathy. Molecular analysis revealed that both sister and brother have the same MECP2 gene mutation; however, their mother does not. This case, as well as other published studies of males with MECP2 mutations, reveals that the clinical manifestations in viable males vary from neonates with severe encephalopathy to adults with mental retardation and demonstrate genotype-phenotype correlations.
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PMID:Rett syndrome: clinical manifestations in males with MECP2 mutations. 1191 64

Rett syndrome (RS) is a progressive neurodevelopmental disorder predominant in females, characterised by mental deficiency, stereotyped hand-washing and apraxia. Notwithstanding the recent identification of the MECP2 gene likely involved in the pathogenesis of SR, the neurobiological bases of this syndrome are still largely unknown. Converging evidence shows that the brain levels of nerve growth factor (NGF), a neurotrophin regulating the development and functioning of central cholinergic neurons, are decreased in RS girls. In this study, the serum levels of NGF were measured in classic RS, in the preserved speech variant (PSV) and in normal controls. Overall analysis failed to evidence significant differences among the three groups. However, whereas NGF levels increased significantly with age in controls, the opposite profile was observed in classic RS, with a progressive age-dependent decrease of NGF. In PSV subjects NGF levels remained constant with age. These findings strengthen the hypothesis of NGF involvement in the pathogenesis of RS.
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PMID:Developmental profile of serum nerve growth factor levels in Rett complex. 1204 31


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