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)

Basic fibroblast growth factor (bFGF) has shown a neurotrophic effect in the neurons of several CNS areas. In vivo, it contributes to restore neurochemical and morphological deficits in different rodent models of brain damage, including rats with brain damage induced by hypoxia/ischemia when FGF was intramuscularly (i.m.) administered. Toxicological and immunological studies performed in rats, mice and volunteers showed no evidence of side-effects. Bovine FGF was i.m. administered in children with mental retardation caused by perinatal hypoxia, aged 1-15 years, at dosages of 0.4 or 0.28 microgram kg-1, once or twice a month, over 7-12 months. Group A [n = 12; 6 treated (T), 6 controls (Ct)], group B (n = 16; 8 T, 8 Ct) and group C (n = 67; 45 T, 22 Ct) were evaluated with the P. A. R. scale, the WISC-RM and the Gesell scale, respectively. Development increased significantly in treated children from groups A (P < 0.02) and C (P < 0.001), and IQ rose by more than 10 points (P < 0.001) in group B patients.
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PMID:Psychometric analysis in children with mental retardation due to perinatal hypoxia treated with fibroblast growth factor (FGF) and showing improvement in mental development. 812 97

The Ras/MAPK pathway is critical for human development and plays a central role in the formation and progression of most cancers. Children born with germ-line mutations in BRAF, MEK1 or MEK2 develop cardio-facio-cutaneous (CFC) syndrome, an autosomal dominant syndrome characterized by a distinctive facial appearance, heart defects, skin and hair abnormalities and mental retardation. CFC syndrome mutations in BRAF promote both kinase-activating and kinase-impaired variants. CFC syndrome has a progressive phenotype, and the availability of clinically active inhibitors of the MAPK pathway prompts the important question as to whether such inhibitors might be therapeutically effective in the treatment of CFC syndrome. To study the developmental effects of CFC mutant alleles in vivo, we have expressed a panel of 28 BRAF and MEK alleles in zebrafish embryos to assess the function of human disease alleles and available chemical inhibitors of this pathway. We find that both kinase-activating and kinase-impaired CFC mutant alleles promote the equivalent developmental outcome when expressed during early development and that treatment of CFC-zebrafish embryos with inhibitors of the FGF-MAPK pathway can restore normal early development. Importantly, we find a developmental window in which treatment with a MEK inhibitor can restore the normal early development of the embryo, without the additional, unwanted developmental effects of the drug.
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PMID:Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development and are sensitive to small molecule inhibitors. 1937 13

Sotos syndrome (SoS) is characterized by tall stature, characteristic craniofacial features and mental retardation. It is caused by haploinsufficiency of the NSD1 gene. In this study, our objective was to identify downstream effectors of NSD1 and to map these effectors in signaling pathways associated with growth. Genome-wide expression studies were performed on dermal fibroblasts from SoS patients with a confirmed NSD1 abnormality. To substantiate those results, phosphorylation, siRNA and transfection experiments were performed. A significant association was demonstrated with the Mitogen-Activated Protein Kinase (MAPK) pathway. Members of the fibroblast growth factor family such as FGF4 and FGF13 contributed strongly to the differential expression in this pathway. In addition, a diminished activity state of the MAPK/ERK pathway was demonstrated in SoS. The Ras Interacting Protein 1 (RASIP1) was identified to exhibit upregulated expression in SoS. It was shown that RASIP1 dose-dependently potentiated bFGF induced expression of the MAPK responsive SBE reporter providing further support for a link between NSD1 and the MAPK/ERK signaling pathway. Additionally, we demonstrated NSD1 expression in the terminally differentiated hypertrophic chondrocytes of normal human epiphyseal growth plates. In short stature syndromes such as hypochondroplasia and Noonan syndrome, the activation level of the FGF-MAPK/ERK-pathway in epiphyseal growth plates is a determining factor for statural growth. In analogy, we propose that deregulation of the MAPK/ERK pathway in SoS results in altered hypertrophic differentiation of NSD1 expressing chondrocytes and may be a determining factor in statural overgrowth and accelerated skeletal maturation in SoS.
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PMID:Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway. 2315 69