title: Reduced cyclic AMP production in fragile X syndrome: cytogenetic and molecular correlations.
abstract: 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.
authors.affiliation: Department of Pediatrics, RUSH-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
authors.forename: E
authors.initials: E
authors.lastname: Berry-Kravis
authors.forename: M
authors.initials: M
authors.lastname: Hicar
authors.forename: R
authors.initials: R
authors.lastname: Ciurlionis
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000097:blood* / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins
chemical_list: D000242:Cyclic AMP; D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human