FMRP expression as a potential prognostic indicator in fragile X syndrome

Am J Med Genet. 1999 May 28;84(3):250-61.


Absence or deficit of FMR1 protein (FMRP) resulting from methylation of full mutation genes is the fundamental defect in fragile X syndrome. We used FMRP immunocytochemistry and detailed phenotypic assessment to investigate the relationship between degree of FMRP expression and the broad clinical spectrum of impairment in 80 individuals affected with fragile X syndrome. FMRP expression correlated with IQ in mosaic males (P=0.043), males with a partially methylated full mutation (P=0.0005), and females with a full mutation (P=0.046). In the females, FMRP expression also correlated with the number of fragile X physical features (P=0.0003). Even modest deficits in FMRP result in some manifestations of fragile X syndrome. In this initial study of 53 males, FMRP expression testing had a very high positive predictive value (100%, confidence interval of 29-100%) for a nonretarded IQ among males with expression of FMRP in > or = 50% of lymphocytes (3 males), suggesting that FMRP expression may have potential as a prognostic indicator in males with fragile X syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • DNA / analysis
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Gene Expression / genetics*
  • Humans
  • Immunohistochemistry
  • Infant
  • Linear Models
  • Male
  • Middle Aged
  • Mosaicism / genetics
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • RNA-Binding Proteins*


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