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)

Cyclic AMP production was studied in platelets from 31 patients with fragile X syndrome, 16 patients with mental retardation, 4 patients with autistic disorder, and 57 control individuals. 1-isobutyl-3-methylxanthine (IBMX) was used to inhibit phosphodiesterase; prostaglandin E1 (PGE1), to stimulate cAMP production via a receptor-dependent mechanism, and forskolin (FSK), to directly activate the catalytic subunit. Cyclic AMP production in IBMX, PGE1 + IBMX, and FSK + IBMX was 50% (P < 0.05), 65% (P = 0.001), and 53% (P = 0.001), respectively, in fragile X platelets relative to controls. Cyclic AMP production was not statistically different from controls in patients with mental retardation or autistic disorder. There was no effect of age or sex on cAMP production. Dose response curves suggested that abnormal cAMP production was due to diminished maximal response rather than altered potency of stimulating agents. The data presented here demonstrate that diminished cAMP production exists in platelets from patients with fragile X syndrome. Thus, defective functioning of cAMP-mediated regulatory signalling pathways in fragile X brain may contribute to the mental deficiency in these patients.
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PMID:Demonstration of abnormal cyclic AMP production in platelets from patients with fragile X syndrome. 838 Mar 12

The cAMP cascade is an intracellular signal transduction system thought to be important for neuronal regulation and information storage. cAMP production is reduced in platelets from patients with fragile X syndrome. In the present study we assayed cAMP metabolism, Xq27.3 fragile site percentages, size of amplification mutation in fragile X mental retardation-1 gene (FMR-1), and FMR-1 mRNA levels in 21 lymphoblastoid cell lines (LCL) from fragile X patients. cAMP production was diminished in fragile X LCL relative to controls (n = 20) when cells were assayed in prostaglandin E1 (74%, p < 0.02) and in forskolin (64%, p < 0.1) although the difference was statistically significant only in prostaglandin E1. The length of the FMR-1 amplification mutation correlated with measures of cAMP production which were unassociated with receptor activation (r = -0.53, p = 0.02, and r = -0.48, p = 0.03, for unstimulated and forskolin-stimulated cAMP production, respectively). In fragile X LCL, fragile site percentages did not correlate with any measure of cAMP production. All fragile X LCL showed absence of FMR-1 mRNA. These data suggest that diminished cAMP production in fragile X tissues may be linked to the fragile X amplification mutation, either as a result of influences of the mutation on FMR-1 expression or on transcription of other genes downstream from FMR-1.
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PMID:Reduced cyclic AMP production in fragile X syndrome: cytogenetic and molecular correlations. 855 27