A study of the distributional characteristics of FMR1 transcript levels in 238 individuals

Hum Genet. 2004 Apr;114(5):439-47. doi: 10.1007/s00439-004-1086-x. Epub 2004 Feb 3.


Fragile X syndrome, the most common form of inherited mental retardation, is caused by hyperexpansion and hypermethylation of a CGG repeat tract in the 5' untranslated region of the FMR1 gene. This methylation causes the gene to be transcriptionally silenced. In addition to the common allele form with less than 41 repeats, there are two other allelic forms of the FMR1 gene that are unmethylated: premutation (61-200 CGG repeats) and intermediate (41-60 CGG repeats). Recently, premutation-specific phenotypes not related to fragile X syndrome have been reported: a 20-fold increased risk for premature ovarian failure (POF) among female carriers and an increased risk for a tremor ataxia syndrome (TAS) primarily among older male carriers. At the molecular level, increased levels of FMR1 transcript have been observed among premutation carriers. Increased levels of transcript may be causally related to the POF or TAS phenotypes or may be a surrogate of some other allelic property. In this report, we have examined the distributional properties of transcript levels by repeat size and gender among 238 individuals. We have confirmed a significant linear relationship between transcript level and repeat size in males and females. The evidence for the linear effect is primarily within the premutation size alleles.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Analysis of Variance
  • Ataxia / genetics
  • DNA Primers
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Gene Silencing
  • Humans
  • Male
  • Nerve Tissue Proteins / genetics*
  • Primary Ovarian Insufficiency / genetics
  • RNA, Messenger / genetics*
  • RNA-Binding Proteins*
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trinucleotide Repeat Expansion / genetics*


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