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 report an unusual case with mental retardation, short stature, sparse scalp hair, prominence of scalp veins, atrophy of subcutaneous fat, pterygia of the neck and loose skin. The patient excreted greater amounts of low-sulphated chondroitin sulphate (LSC) in the urine than age-matched controls. The pattern of glycosaminoglycan in serum and its synthesis by the patient fibroblasts were normal. Collagen, elastin and decorin mRNA levels in the patient fibroblasts were also unaltered. These results suggest that this patient seems to be different from Lowe's syndrome and decorin-deficient progeroid. An abnormal LSC metabolism may be partially responsible for the pathology of these syndromes.
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PMID:Overexcretion of low-sulphated chondroitin sulphate in the urine of the patient resembling progeroid. 940 87

Down syndrome (DS) is the most common human chromosomal abnormality caused by an extra copy of chromosome 21 and characterized clinically by somatic anomalies, mental retardation and precocious dementia. The phenotype of DS is thought to result from overexpression of a gene or genes located on the triplicated chromosome or chromosome region. Reports that challenge this notion, however, have been published. To add to this body of evidence, the expression of beta-amyloid precursor protein (APP), ETS-2 and collagen alpha1 (VI) chain precursor, encoded on chromosome 21, was investigated in fetal brain by western blot and two-dimensional electrophoresis (2-DE). Western blot detected APP and ETS-2 that migrated at approximately 75 and 50kDa, respectively. Subsequent densitometric analysis of APP and ETS-2 immunoreactivity did not produce any significant change between controls and DS. Since the metabolic fate of APP determines the propensity of amyloid beta production, the expression of the secreted forms of APP (sAPP) had been examined. Neither the expression of sAPPalpha nor sAPPbeta showed any detectable changes among the two groups. Collagen alpha1 (VI) chain precursor, a protein resolved as a single spot on 2D gel was identified by matrix associated laser desorption ionization mass spectroscopy. Quantitative analysis of this spot using the 2D Image Master software revealed a significant decrease in fetal DS (P < 0.01) compared to controls. Linear regression analysis did not show any correlation between protein levels and age. The current data suggest that overexpression per se can not fully explain the DS phenotype.
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PMID:Beta-amyloid precursor protein, ETS-2 and collagen alpha 1 (VI) chain precursor, encoded on chromosome 21, are not overexpressed in fetal Down syndrome: further evidence against gene dosage effect. 1177 56

Foetal Alcohol Syndrome is observed in 2/1000 live births worldwide and is characterized by decreased pre-natal and postnatal growth, physical anomalies and mental retardation. To determine the effects of ethanol (Et) on foetal cells cultured in the absence of hormones or growth factors, human foetal lung (HFL1) fibroblasts were exposed to Et-supplemented media (0.1-2% Et) for 6 hr to 7 days. Growth rates, thymidine incorporation into DNA, protein synthesis and degradation, and collagen production were assessed. For growth experiments, cells were seeded at 1 3 confluent density and incubated in Et-supplemented medium 24 hr later. Metabolic labelling was performed on confluent monolayers using [(3)H]thymidine (TdR), [(3)H]leucine or [(3)H]proline. Exposure to Et for 3 or 7 days decreased cell numbers but normal proliferation resumed when cells were re-plated in control medium. Exposure to 0.5% Et for 7 days resulted in a 3.5-fold increase in [(3)H]TdR uptake. Et suppressed protein production and enhanced degradation. The most significant decrease was seen at 6 hr, but was influenced by the amino acid used for labelling. Agarose-gel chromatography suggests that Et preferentially alters the lower-molecular-weight species. The percentage of the total protein secreted into the medium was not changed. Collagen production, as a percentage of total protein, decreased after a 48-hr label and a 7-day incubation with Et. The percentage of total collagen that was secreted into the medium was also not influenced by Et. The results indicate that, in the absence of endocrine or nutritional manipulation, acute exposure to Et in vitro inhibits cell growth and protein production; protein secretion, however, remains intact.
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PMID:Temporal effects of ethanol on growth, thymidine uptake, protein and collagen production in human foetal lung fibroblasts. 2070 77

Dyggve-Melchior-Clausen syndrome (DMC), a severe autosomal recessive skeletal disorder with mental retardation, is caused by mutation of the gene encoding Dymeclin (DYM). Employing patient fibroblasts with mutations characterized at the genomic and, for the first time, transcript level, we identified profound disruption of Golgi organization as a pathogenic feature, resolved by transfection of heterologous wild-type Dymeclin. Collagen targeting appeared defective in DMC cells leading to near complete absence of cell surface collagen fibers. DMC cells have an elevated apoptotic index (P< 0.01) likely due to a stress response contingent upon Golgi-related trafficking defects. We performed spatiotemporal mapping of Dymeclin expression in zebrafish embryos and identified high levels of transcript in brain and cartilage during early development. Finally, in a chondrocyte cDNA library, we identified two novel secretion pathway proteins as Dymeclin interacting partners: GOLM1 and PPIB. Together these data identify the role of Dymeclin in secretory pathways essential to endochondral bone formation during early development.
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PMID:Dymeclin, the gene underlying Dyggve-Melchior-Clausen syndrome, encodes a protein integral to extracellular matrix and golgi organization and is associated with protein secretion pathways critical in bone development. 2128 Jan 49