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)

Thirty-four symptomatic cases of inherited transcobalamin II (TCII) deficiency were analysed in order to determine the frequency and nature of neurologic manifestations. In no instance was there definite evidence of a neurologic disorder at the time of presentation as a young infant. One child of 2 1/2 years transiently lost deep tendon reflexes at a time of suboptimal treatment. A syndrome of mental retardation and other neurologic manifestations was observed in three cases, all with the following in common: (1) an extended duration of illness of 2-17 years; (2) inadequate or not treatment with Cbl; (3) treatment with folic of folinic acid. TCII deficiency rarely if ever presents with neurologic manifestations. However, neurologic disorders can be produced subsequently by improper treatment.
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PMID:The neurologic aspects of transcobalamin II deficiency. 153 99

The Cool-2 (cloned-out of library-2) protein (identical to alpha-Pix for Pak-interactive exchange factor) has been implicated in various biological responses including chemoattractant signaling and in certain forms of mental retardation. We show that when Cool-2 exists as a dimer, it functions as a Rac-specific guanine nucleotide exchange factor (GEF). Dimerization of Cool-2 enables its Dbl (diffuse B-cell lymphoma) and pleckstrin homology domains to work together (in trans) to bind specifically to Rac-GDP. Dissociation of dimeric Cool-2 into its monomeric form allows it to act as a GEF for Cdc42 as well as for Rac. The binding of either PAK (p21-activated kinase) or Cbl (Casitas B-lymphoma) to the SH3 domain of monomeric Cool-2 is necessary for the functional interactions between GDP-bound Cdc42 or Rac and the Cool-2 monomer. The betagamma subunit complex of large GTP-binding proteins, by interacting with PAK, stimulates the dissociation of the Cool-2 dimer and activates its GEF activity for Cdc42. Overall, these findings highlight novel mechanisms by which extracellular signals can direct the specific activation of Rac versus Cdc42 by Cool-2/alpha-Pix.
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PMID:Novel regulatory mechanisms for the Dbl family guanine nucleotide exchange factor Cool-2/alpha-Pix. 1530 50