Reduced cyclic AMP production in fragile X syndrome: cytogenetic and molecular correlations

Pediatr Res. 1995 Nov;38(5):638-43. doi: 10.1203/00006450-199511000-00002.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Cyclic AMP / metabolism*
  • DNA / metabolism
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / blood*
  • Fragile X Syndrome / genetics
  • Gene Amplification
  • Humans
  • Lymphocytes / cytology
  • Male
  • Middle Aged
  • Mutation
  • Nerve Tissue Proteins / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins*


  • FMR1 protein, human
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein
  • DNA
  • Cyclic AMP