Tissue heterogeneity of the FMR1 mutation in a high-functioning male with fragile X syndrome

Annette K. Taylor, Flora Tassone, Pamela N. Dyer, Steven M. Hersch, Jennifer B. Harris, William T. Greenough, Randi J Hagerman

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Few studies have been conducted comparing the FMR1 mutation in multiple tissues of individuals affected with fragile X syndrome. We report a postmortem study of the FMR1 mutation in multiple tissues from a high- functioning male with fragile X syndrome. This man was not mentally retarded and had only a few manifestations of the disorder such as learning disabilities and mild attention problems. Southern blot analysis of leukocytes demonstrated an unmethylated mutation with a wide span of sizes extending from the premutation to full mutation range. A similar pattern was seen in most regions of the brain. In contrast, a methylated full mutation of a single size was seen in the parietal lobe and in most nonbrain tissues studied. Therefore, there were striking differences in both FMR1 mutation size and methylation status between tissues. Lack of mental retardation in this individual may have been due to sufficient expression of FMR1 protein (FMRP) in most areas of the brain. Immunocytochemistry showed FMRP expression in regions of the brain with the unmethylated mutation (superior temporal cortex, frontal cortex, and hippocampus) and no expression in the region with the methylated full mutation (parietal). Neuroanatomical studies showed no dendritic spine pathology in any regions of the brain analyzed.

Original languageEnglish (US)
Pages (from-to)233-239
Number of pages7
JournalAmerican Journal of Medical Genetics
Issue number3
StatePublished - May 28 1999
Externally publishedYes


  • Autopsy
  • FMR1 mutation
  • Fragile X syndrome
  • High functioning
  • Methylation
  • Postmortem
  • Tissue heterogeneity
  • Trinucleotide repeat instability
  • Unmethylated full mutation

ASJC Scopus subject areas

  • Genetics(clinical)


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