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)

A systematic investigation of morbidity patterns was conducted in 1977- 80 among 2580 children under 12 years of age attending mobile hospital camps in 4 districts on India's Hamachal Pradesh. The children came from remote villages where socioeconomic and educational levels were low and environmental sanitation was rudimentary. There were 1301 cases of protein energy malnutrition in this group, 124 involving children 0-1 year of age, 514 in the 1-5-year age group, and 663 (51%) in the 5-12- year age group. At the time of examination, 287 of the children were infested with worms and 125 had diarrhea. These 3 conditions-- malnutrition, worm infestation, and diarrhea--were present in 32% of the village children surveyed. The most common form of morbidity was nutritional disorders (malnutrition, anemia, and vitamin deficiencies), affecting 70% of the children. The next most common condition was respiratory infection, affecting 35%. Other disorders affecting significant numbers of children were scabies, pyoderma, convulsions, mental retardation, rheumatic fever and congenital heart diseases, and renal diseases. Morbidity from conditions such as gastroenteritis, measles, and pneumonia was often accompanied by malnutrition. Thus, there is a need in this area for child health programs aimed at providing nutrition education as well as improving immunization coverage.
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PMID:Childhood morbidity in mobile hospital camps in Himachal Pradesh. 262 Sep 84

Cornelia de Lange syndrome (CdLS) is a multiple malformation disorder characterized by dysmorphic facial features, mental retardation, growth delay and limb reduction defects. We indentified and characterized a new gene, NIPBL, that is mutated in individuals with CdLS and determined its structure and the structures of mouse, rat and zebrafish homologs. We named its protein product delangin. Vertebrate delangins have substantial homology to orthologs in flies, worms, plants and fungi, including Scc2-type sister chromatid cohesion proteins, and D. melanogaster Nipped-B. We propose that perturbed delangin function may inappropriately activate DLX genes, thereby contributing to the proximodistal limb patterning defects in CdLS. Genome analyses typically identify individual delangin or Nipped-B-like orthologs in diploid animal and plant genomes. The evolution of an ancestral sister chromatid cohesion protein to acquire an additional role in developmental gene regulation suggests that there are parallels between CdLS and Roberts syndrome.
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PMID:NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome. 1514 85

Down syndrome (DS), as a phenotypic result of trisomy 21, is the most frequent aneuploidy at birth and the most common known genetic cause of mental retardation. DS is also characterized by other phenotypes affecting many organs, including brain, muscle, heart, limbs, gastrointestinal tract, skeleton, and blood. Any of the human chromosome 21 (Hsa21) genes may contribute to some of the DS phenotypes. To determine which of the Hsa21 genes are involved in DS, the effects of disrupting and overexpressing individual human gene orthologs in model organisms, such as the nematode Caenorhabditis elegans, can be analyzed. Here, we isolated and characterized C21orf80 (human chromosome 21 open reading frame 80), a potential novel protein O-fucosyltransferase gene that encodes three alternatively spliced transcripts. Transient expression of tagged C21orf80 proteins suggests a primary intracellular localization in the Golgi apparatus. To gain insight into the biological role of C21orf80 and its potential role in DS, we isolated its C. elegans ortholog, pad-2, and performed RNA interference (RNAi) and overexpression experiments. pad-2(RNAi) embryos showed failure to undergo normal morphogenesis. Transgenic worms with elevated dosage of pad-2 displayed severe body malformations and abnormal neuronal development. These results show that pad-2 is required for normal development and suggest potential roles for C21orf80 in the pathogenesis of DS.
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PMID:The Caenorhabditis elegans ortholog of C21orf80, a potential new protein O-fucosyltransferase, is required for normal development. 1523 96

miRNAs are reported to sequence-specifically control the translation of target mRNAs by binding to 3 UTRs. The abundant expression of miRNAs in the brain highlights their biological significance in neurodevelopment. Many studies have shown that miRNAs are involved in a variety of functions, including developmental transitions and neuronal patterning, apoptosis, fat metabolism and regulation of hematopoietic lineage differentiation in different organisms. miRNAs act as regulatory switches in the determination of developmental fate through their distinct patterns of expression. The tissue-specific expression of miRNAs during brain development could possibly direct the development of cells in different subtypes. Several miRNAs are localized to neuronal subtypes and exhibit a more diverse or specific expression pattern within various neuronal cell types such as glial cells and neuronal progenitor cells. Perturbations in the expression pattern of miRNAs could lead to defects in human brain development and neurological disorders. The bioinformatic prediction tools suggest that some genes involved in synaptic formations and mental retardation are putative targets for miRNAs. miRNAs have been shown to specify cell fates in the nervous system of worms and brain morphogenesis in fish, and their distinct expression patterns during mammalian brain development. This suggests a potential role of miRNAs in neurodevelopment of mammals and other organisms. In this review, I have focused on the role of miRNAs in brain development and possible neurological disorders.
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PMID:miRNAs: from neurogeneration to neurodegeneration. 1771 30

Metallophosphoesterase-domain-containing protein 2 (MPPED2) is a highly evolutionarily conserved protein with orthologs found from worms to humans. The human MPPED2 gene is found in a region of chromosome 11 that is deleted in patients with WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome, and MPPED2 may function as a tumor suppressor. However, the precise cellular roles of MPPED2 are unknown, and its low phosphodiesterase activity suggests that substrate hydrolysis may not be its prime function. We present here the structures of MPPED2 and two mutants, which show that the poor activity of MPPED2 is not only a consequence of the substitution of an active-site histidine residue by glycine but also due to binding of AMP or GMP to the active site. This feature, enhanced by structural elements of the protein, allows MPPED2 to utilize the conserved phosphoprotein-phosphatase-like fold in a unique manner, ensuring that its enzymatic activity can be combined with a possible role as a scaffolding or adaptor protein.
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PMID:Unique utilization of a phosphoprotein phosphatase fold by a mammalian phosphodiesterase associated with WAGR syndrome. 2182 79

Neuroligins are cell adhesion proteins that interact with neurexins at the synapse. This interaction may contribute to differentiation, plasticity and specificity of synapses. In humans, single mutations in neuroligin encoding genes lead to autism spectrum disorder and/or mental retardation. Caenorhabditis elegans mutants deficient in nlg-1, an orthologue of human neuroligin genes, have defects in different behaviors. Here we show that the expression of human NLGN1 or rat Nlgn1 cDNAs in C. elegans nlg-1 mutants rescues the fructose osmotic strength avoidance and gentle touch response phenotypes. Two specific point mutations in NLGN3 and NLGN4 genes, involved in autistic spectrum disorder, were further characterized in this experimental system. The R451C allele described in NLGN3, was analyzed with both human NLGN1 (R453C) and worm NLG-1 (R437C) proteins, and both were not functional in rescuing the osmotic avoidance behavior and the gentle touch response phenotype. The D396X allele described in NLGN4, which produces a truncated protein, was studied with human NLGN1 (D432X) and they did not rescue any of the behavioral phenotypes analyzed. In addition, RNAi feeding experiments measuring gentle touch response in wild type strain and worms expressing SID-1 in neurons (which increases the response to dsRNA), both fed with bacteria expressing dsRNA for nlg-1, provided evidence for a postsynaptic in vivo function of neuroligins both in muscle cells and neurons, equivalent to that proposed in mammals. This finding was further confirmed generating transgenic nlg-1 deficient mutants expressing NLG-1 under pan-neuronal (nrx-1) or pan-muscular (myo-3) specific promoters. All these results suggest that the nematode could be used as an in vivo model for studying particular synaptic mechanisms with proteins orthologues of humans involved in pervasive developmental disorders.
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PMID:Functional phenotypic rescue of Caenorhabditis elegans neuroligin-deficient mutants by the human and rat NLGN1 genes. 2272 84

Toxocara canis is a parasitic nematode that infects canines worldwide, and as a consequence of the widespread environmental dissemination of its ova in host faeces, other abnormal hosts including mice and humans are exposed to infection. In such abnormal or paratenic hosts, the immature third-stage larvae undergo a somatic migration through the organs of the body but fail to reach maturity as adult worms in the intestine. The presence of the migrating larvae contributes to pathology that is dependent upon the intensity of infection and the location of the larvae. A phenomenon of potential public health significance in humans and of ecological significance in mice is that T. canis larvae exhibit neurotrophic behaviour, which results in a greater concentration of parasites in the brain, as infection progresses. Toxocara larval burdens vary between individual outbred mice receiving the same inocula, suggesting a role for immunity in the establishment of cerebral infection. Although the systemic immune response to T. canis has been widely reported, the immune response in the brain has received little attention. Differential cytokine expression and other brain injury-associated biomarkers have been observed in infected versus uninfected outbred and inbred mice. Preliminary data have also suggested a possible link between significant memory impairment and cytokine production associated with T. canis infection. Mice provide a useful, replicable animal model with significant applicability and ease of manipulation. Understanding the cerebral host-parasite relationship may shed some light on the cryptic symptoms of human infection where patients often present with other CNS disorders such as epilepsy and mental retardation.
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PMID:The significance of cerebral toxocariasis: a model system for exploring the link between brain involvement, behaviour and the immune response. 2322 70

PHF8 is a JmjC domain-containing histone demethylase, defects in which are associated with X-linked mental retardation. In this study, we examined the roles of two PHF8 homologs, JMJD-1.1 and JMJD-1.2, in the model organism C. elegans in response to DNA damage. A deletion mutation in either of the genes led to hypersensitivity to interstrand DNA crosslinks (ICLs), while only mutation of jmjd-1.1 resulted in hypersensitivity to double-strand DNA breaks (DSBs). In response to ICLs, JMJD-1.1 did not affect the focus formation of FCD-2, a homolog of FANCD2, a key protein in the Fanconi anemia pathway. However, the dynamic behavior of RPA-1 and RAD-51 was affected by the mutation: the accumulations of both proteins at ICLs appeared normal, but their subsequent disappearance was retarded, suggesting that later steps of homologous recombination were defective. Similar changes in the dynamic behavior of RPA-1 and RAD-51 were seen in response to DSBs, supporting a role of JMJD-1.1 in homologous recombination. Such a role was also supported by our finding that the hypersensitivity of jmjd-1.1 worms to ICLs was rescued by knockdown of lig-4, a homolog of Ligase 4 active in nonhomologous end-joining. The hypersensitivity of jmjd-1.1 worms to ICLs was increased by rad-54 knockdown, suggesting that JMJD-1.1 acts in parallel with RAD-54 in modulating chromatin structure. Indeed, the level of histone H3 Lys9 tri-methylation, a marker of heterochromatin, was higher in jmjd-1.1 cells than in wild-type cells. We conclude that the histone demethylase JMJD-1.1 influences homologous recombination either by relaxing heterochromatin structure or by indirectly regulating the expression of multiple genes affecting DNA repair.
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PMID:A PHF8 homolog in C. elegans promotes DNA repair via homologous recombination. 2585 98