Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children who are born in a community with insufficient micronutrients, particularly iodine in remote rural areas are associated with low intellectual functions and mental retardation. The aim of this cross-sectional study is to determine the mental performance of the schoolchildren in Bario, a highland settlement of the Kelabit people in the district of Baram, Sarawak and to determine its correlation with the availability of iodine in the environment, as well as other micronutrients such as selenium, copper and manganese. A total of 25 schoolchildren in Bario age ranging from 7 to 12 years old participated in the study. Mental performance of the schoolchildren were tested using TONI-2 (Test of Nonverbal Intelligence--second edition), a cognitive ability measures with a response format which eliminates language and reduces motoric and cultural factors. The iodine levels from several wells, soils and salt found in Bario were determined using HPLC (software version 3.05.01) whilst serum levels of selenium, copper and manganese were measured using Graphite Furnace Atomic Absorption Spectrophotometer (GFAAS). The results showed that the median and mode scores of intelligence quotient for Bario were 82 and 75, respectively, whilst median and mode scores of intelligence percentile were 11.0 and 5.0, respectively. The maximum score achieved were at the average level with the quotient score between 90-110. It was found that salt produced from one of the wells in Bario contained high quantity of iodine. Based on standards established by the Trace Elements Laboratory, Roben Institute, University of Surrey, United Kingdom, schoolchildren in Bario are having sufficient blood levels of copper and a high selenium and manganese levels. Despite the remoteness of the study area, the schoolchildren in Bario, Sarawak showed higher mental performance compared to other isolated areas. This is probably correlated with the high micronutrients availability, particularly iodine, found naturally in Bario.
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PMID:Micronutrients and its correlation with mental performance among schoolchildren in Bario, Sarawak: a preliminary study. 1475 Mar 69

Mediator occupies a central role in RNA polymerase II transcription as a sensor, integrator, and processor of regulatory signals that converge on protein-coding gene promoters. Compared to its role in gene activation, little is known regarding the molecular mechanisms and biological implications of Mediator as a transducer of repressive signals. Here we describe a protein interaction network required for extraneuronal gene silencing comprising Mediator, G9a histone methyltransferase, and the RE1 silencing transcription factor (REST; also known as neuron restrictive silencer factor, NRSF). We show that the MED12 interface in Mediator links REST with G9a-dependent histone H3K9 dimethylation to suppress neuronal genes in nonneuronal cells. Notably, missense mutations in MED12 causing the X-linked mental retardation (XLMR) disorders FG syndrome and Lujan syndrome disrupt its REST corepressor function. These findings implicate Mediator in epigenetic restriction of neuronal gene expression to the nervous system and suggest a pathologic basis for MED12-associated XLMR involving impaired REST-dependent neuronal gene regulation.
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PMID:Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation. 1869 61

The molecular mechanisms that lead to the cognitive defects characteristic of Down syndrome (DS), the most frequent cause of mental retardation, have remained elusive. Here we use a transgenic DS mouse model (152F7 line) to show that DYRK1A gene dosage imbalance deregulates chromosomal clusters of genes located near neuron-restrictive silencer factor (REST/NRSF) binding sites. We found that Dyrk1a binds the SWI/SNF complex known to interact with REST/NRSF. The mutation of a REST/NRSF binding site in the promoter of the REST/NRSF target gene L1cam modifies the transcriptional effect of Dyrk1a-dosage imbalance on L1cam. Dyrk1a dosage imbalance perturbs Rest/Nrsf levels with decreased Rest/Nrsf expression in embryonic neurons and increased expression in adult neurons. Using transcriptome analysis of embryonic brain subregions of transgenic 152F7 mouse line, we identified a coordinated deregulation of multiple genes that are responsible for dendritic growth impairment present in DS. Similarly, Dyrk1a overexpression in primary mouse cortical neurons induced severe reduction of the dendritic growth and dendritic complexity. We propose that DYRK1A overexpression-related neuronal gene deregulation via disturbance of REST/NRSF levels, and the REST/NRSF-SWI/SNF chromatin remodelling complex, significantly contributes to the neural phenotypic changes that characterize DS.
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PMID:DYRK1A interacts with the REST/NRSF-SWI/SNF chromatin remodelling complex to deregulate gene clusters involved in the neuronal phenotypic traits of Down syndrome. 1921 69

Genomic and proteomic studies of neurodegenerative disorders require complementary approaches to integrate the massive amount of data generated in high throughput experimental procedures. We propose a Bioinformatics pipeline in which expression studies guide the selection of candidate genes that should be screened for potential new genetic variations from a public expressed site tags (ESTs) database. Motivated by the former interest of our group in genetic polymorphisms involved with the immune system, we selected five genes from a previous expression microarrays study of hippocampal cornu ammonis (CA1) area of Alzheimer's Disease subjects (AD). The CLCbio Workbench Combined version 3.6.2. was initially used to build ESTs and mRNA files retrieved respectively from the Goldenpath of University of California Santa Cruz (UCSC) and National Center for Biotechnology Information (NCBI) databases and latter to perform multiple batches of Smith-Waterman alignments. A total of 116 ESTs sequences were selected after proper stringent parameters were applied to the first set of mismatches. The annotation revealed various classes of variations, most of them deletions (176). Amongst this specific group, some were frameshift deletions (35) and the virtual translation of a few others (5) were predicted to induce no change other than a single aminoacid removal, with no subsequent repercussions at the protein sequence. In addition, the analysis identified transitions (three), transversions (52), synonymous (41), non-synonymous (12), and deletions in 36 ESTs located in Untranslated Regions -UTRs (Supplementary data). Deletions are often associated to major genetics syndromes with dysmorphic features. However, various recent studies show that common microdeletions might be highly associated with common neuropsychiatric disorders such as schizophrenia, autism, mental retardation, or even in various ethnicities, detected in whole genome sequencing experiments. A virtual validation confirmed that some of the variations identified were previously reported and confirmed in DNA samples, showing that this method is a feasible way to detect genetic variations that merit further exploration in AD genetic risk factor association studies.
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PMID:In silico identification of new genetic variations as potential risk factors for Alzheimer's disease in a microarray-oriented simulation. 1929 Apr 94