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)

We describe a female infant with multiple congenital anomalies and mental retardation, pre- and postnatal growth failure, microcephaly, unusual facial appearance, and minor skeletal anomalies, all very suggestive of the partial trisomy 20(p) syndrome. Although she was born to karyotypically normal parents, she had an extra small metacentric chromosome. Analysis of metaphase and prometaphase chromosomes by GTG banding and Giemsa 11 staining showed that the extra chromosome was a number 20 with a deletion of the distal end of the long arm. Gene dose studies of adenosine deaminase (ADA) and inosine triphosphatase (ITP) supported the cytogenetic interpretation.
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PMID:Partial trisomy 20 confirmed by gene dosage studies. 23 7

Down syndrome (DS) is the most frequent genetic disorder with mental retardation and caused by trisomy 21. Although the gene dosage effect hypothesis has been proposed to explain the impact of extra chromosome 21 on the pathology of DS, a series of evidence that challenge this hypothesis has been reported. The availability of the complete sequences of genes on chromosome 21 serves now as starting point to find functional information of the gene products, but information on gene products is limited so far. We therefore evaluated expression levels of six proteins whose genes are encoded on chromosome 21 (synaptojanin-1, chromosome 21 open reading frame 2, oligomycin sensitivity confering protein, peptide 19, cystatin B and adenosine deaminase RNA-specific 2) in fetal cerebral cortex from DS and controls at 18-19 weeks of gestational age using Western blot analysis. Synaptojanin-1 and C21orf2 were increased in DS, but others were comparable between DS and controls, suggesting that the DS phenotype cannot be simply explained by gene dosage effects. We are systematically quantifying all proteins whose genes are encoded on chromosome 21 in order to provide a better understanding of the pathobiochemistry of DS at the protein level. These studies are of significance as they show for the first time protein levels that are carrying out specific function in human fetal brain with DS.
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PMID:Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: challenging the gene dosage effect hypothesis (Part III). 1262 44

Fragile X syndrome (FXS) is the most frequent inherited form of mental retardation. The cause for this X-linked disorder is the silencing of the fragile X mental retardation 1 (fmr1) gene and the absence of the fragile X mental retardation protein (Fmrp). The RNA-binding protein Fmrp represses protein translation, particularly in synapses. In Drosophila, Fmrp interacts with the adenosine deaminase acting on RNA (Adar) enzymes. Adar enzymes convert adenosine to inosine (A-to-I) and modify the sequence of RNA transcripts. Utilizing the fmr1 zebrafish mutant (fmr1-/-), we studied Fmrp-dependent neuronal circuit formation, behavior, and Adar-mediated RNA editing. By combining behavior analyses and live imaging of single axons and synapses, we showed hyperlocomotor activity, as well as increased axonal branching and synaptic density, in fmr1-/- larvae. We identified thousands of clustered RNA editing sites in the zebrafish transcriptome and showed that Fmrp biochemically interacts with the Adar2a protein. The expression levels of the adar genes and Adar2 protein increased in fmr1-/- zebrafish. Microfluidic-based multiplex PCR coupled with deep sequencing showed a mild increase in A-to-I RNA editing levels in evolutionarily conserved neuronal and synaptic Adar-targets in fmr1-/- larvae. These findings suggest that loss of Fmrp results in increased Adar-mediated RNA editing activity on target-specific RNAs, which, in turn, might alter neuronal circuit formation and behavior in FXS.
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PMID:Fmrp Interacts with Adar and Regulates RNA Editing, Synaptic Density and Locomotor Activity in Zebrafish. 2663 67

In recent years, a substantial body of evidence has emerged demonstrating that purine and pyrimidine synthesis and metabolism play major roles in controlling embryonic and fetal development and organogenesis. Dynamic and time-dependent changes in the expression of purine metabolizing enzymes (such as ectonucleotidases and adenosine deaminase) represent a key checkpoint for the correct sequential generation of the different signaling molecules, that in turn activate their specific membrane receptors. In neurodevelopment, Ca2+ release from radial glia mediated by P2Y1 purinergic receptors is fundamental to allow neuroblast migration along radial glia processes, and their correct positioning in the different layers of the developing neocortex. Moreover, ATP is involved in the development of synaptic transmission and contributes to the establishment of functional neuronal networks in the developing brain. Additionally, several purinergic receptors (spanning from adenosine to P2X and P2Y receptor subtypes) are differentially expressed by neural stem cells, depending on their maturation stage, and their activation tightly regulates cell proliferation and differentiation to either neurons or glial cells, as well as their correct colonization of the developing telencephalon. The purinergic control of neurodevelopment is not limited to prenatal life, but is maintained in postnatal life, when it plays fundamental roles in controlling oligodendrocyte maturation from precursors and their terminal differentiation to fully myelinating cells. Based on the above-mentioned and other literature evidence, it is now increasingly clear that any defect altering the tight regulation of purinergic transmission and of purine and pyrimidine metabolism during pre- and post-natal brain development may translate into functional deficits, which could be at the basis of severe pathologies characterized by mental retardation or other disturbances. This can occur either at the level of the recruitment and/or signaling of specific nucleotide or nucleoside receptors or through genetic alterations in key steps of the purine salvage pathway. In this review, we have provided a critical analysis of what is currently known on the pathophysiological role of purines and pyrimidines during brain development with the aim of unveiling new future strategies for pharmacological intervention in different neurodevelopmental disorders.
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PMID:Pathophysiological Role of Purines and Pyrimidines in Neurodevelopment: Unveiling New Pharmacological Approaches to Congenital Brain Diseases. 2937 73