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 maternally transmitted genomic-imprinting syndrome of mental retardation, hypotonia, and unique dysmorphism with elongated face. We mapped the disease-associated locus to approximately 7.27 Mb on chromosome 8q24 and demonstrated that the disease is caused by a missense mutation in the maternal copy of KCNK9 within this locus. KCNK9 is maternally transmitted (imprinted with paternal silencing) and encodes K(2P)9.1, a member of the two pore-domain potassium channel (K(2P)) subfamily. The mutation fully abolishes the channel's currents--both when functioning as a homodimer or as a heterodimer with K(2P)3.1.
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PMID:Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9. 1867 20

Down's syndrome neurophenotypes are characterized by mental retardation and a decreased brain volume. To identify whether deficits in proliferation could be responsible for this phenotype, neural progenitor cells were isolated from the developing E14 neocortex of Down's syndrome partial trisomy Ts1Cje mice and euploid (WT) littermates and grown as neurospheres. Ts1Cje neural progenitors proliferated at a slower rate, because of a longer cell cycle, and a greater number of cells were positive for glial fibrillary acidic protein. An increase in cell death was also noted. Gene expression profiles of neural progenitor cells from Ts1Cje and WT showed that 54% of triploid genes had expression ratios (Ts1Cje/WT) significantly greater than the expected diploid gene ratio of 1.0. Some diploid genes associated with proliferation, differentiation, and glial function were dysregulated. Interestingly, proliferation and gene expression dysregulation detected in the Ts1Cje mice did not require overexpression of the chromosome 21 genes amyloid precursor protein (App) and soluble superoxide dismutase 1 (Sod1).
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PMID:Proliferation deficits and gene expression dysregulation in Down's syndrome (Ts1Cje) neural progenitor cells cultured from neurospheres. 1947 21

Transcription factor TCF4 (alias ITF2, SEF2 or E2-2) is a broadly expressed basic helix-loop-helix (bHLH) protein that functions as a homo- or heterodimer. Missense, nonsense, frame-shift and splice-site mutations as well as translocations and large deletions encompassing TCF4 gene cause Pitt-Hopkins syndrome (PTHS), a rare developmental disorder characterized by severe motor and mental retardation, typical facial features and breathing anomalies. Irrespective of the mutation, TCF4 haploinsufficiency has been proposed as an underlying mechanism for PTHS. We have recently demonstrated that human TCF4 gene is transcribed using numerous 5' exons. Here, we re-evaluated the impact of all the published PTHS-associated mutations, taking into account the diversity of TCF4 isoforms, and assessed how the reading frame elongating and missense mutations affect TCF4 functions. Our analysis revealed that not all deletions and truncating mutations in TCF4 result in complete loss-of-function and the impact of reading frame elongating and missense mutations ranges from subtle deficiencies to dominant-negative effects. We show that (i) missense mutations in TCF4 bHLH domain and the reading frame elongating mutation damage DNA-binding and transactivation ability in a manner dependent on dimer context (homodimer versus heterodimer with ASCL1 or NEUROD2); (ii) the elongating mutation and the missense mutation at the dimer interface of the HLH domain destabilize the protein; and (iii) missense mutations outside of the bHLH domain cause no major functional deficiencies. We conclude that different PTHS-associated mutations impair the functions of TCF4 by diverse mechanisms and to a varying extent, possibly contributing to the phenotypic variability of PTHS patients.
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PMID:Pitt-Hopkins syndrome-associated mutations in TCF4 lead to variable impairment of the transcription factor function ranging from hypomorphic to dominant-negative effects. 2246 Feb 24

Sarcosine is an N-methyl derivative of the amino acid glycine, and its elevation in tissues and physiological fluids of patients with sarcosinemia could reflect a deficient pool size of activated 1-carbon units. Sarcosinemia is a rare inherited metabolic condition associated with mental retardation. In the present study, we investigated the acute effect of sarcosine and/or creatine plus pyruvate on some parameters of oxidative stress and energy metabolism in cerebral cortex homogenates of 21-day-old Wistar rats. Acute administration of sarcosine induced oxidative stress and diminished the activities of adenylate kinase, GAPDH, complex IV, and mitochondrial and cytosolic creatine kinase. On the other hand, succinate dehydrogenase activity was enhanced in cerebral cortex of rats. Moreover, total sulfhydryl content was significantly diminished, while DCFH oxidation, TBARS content, and activities of SOD and GPx were significantly enhanced by acute administration of sarcosine. Co-administration of creatine plus pyruvate was effective in the prevention of alterations provoked by sarcosine administration on the oxidative stress and the enzymes of phosphoryltransfer network. These results indicate that acute administration of sarcosine may stimulate oxidative stress and alter the energy metabolism in cerebral cortex of rats. In case these effects also occur in humans, they may contribute, along with other mechanisms, to the neurological dysfunction of sarcosinemia, and creatine and pyruvate supplementation could be beneficial to the patients.
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PMID:Evaluation of Oxidative Stress Parameters and Energy Metabolism in Cerebral Cortex of Rats Subjected to Sarcosine Administration. 2735 17


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