Absence of FMR-1 gene expression can be detected with RNA extracted from dried blood specimens

Hum Genet. 1994 May;93(5):488-93. doi: 10.1007/BF00202810.


Fragile X syndrome is a genetic disorder caused by abnormal function of the FMR-1 gene. The majority of fragile X syndrome patients carry an expansion of the CGG tri-nucleotide repeat in the FMR-1 gene, whereas others have a deletion or a point mutation in the FMR-1 structural gene. In this report, we analyzed a typical family with three male patients. RNA from Epstein-Barr virus transformed lymphoblastoid cells was used for RNase protection assay and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Five normal individuals and one asymptomatic heterozygote from this family expressed detectable FMR-1 transcripts, whereas three fragile X patients showed no sign of expression with either assay. To extend the application of this PCR-based assay to laboratory diagnosis of fragile X syndrome, we confirmed that dried blood samples collected on screening filter papers for newborns are an adequate source of RNA for RT-PCR. Moreover, fragile X patients from the study family and another family were reliably identified by the absence of the FMR-1-specific PCR product from the dried blood specimens. Our studies indicate that this simple assay can be used to diagnose the fragile X syndrome for the majority of male patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blood Preservation
  • Cell Transformation, Viral
  • Cells, Cultured
  • DNA Primers / chemistry
  • DNA Primers / genetics
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / blood*
  • Fragile X Syndrome / genetics*
  • Gene Deletion*
  • Gene Expression
  • Humans
  • Infant, Newborn
  • Male
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Polymerase Chain Reaction
  • RNA / blood*
  • RNA / isolation & purification
  • RNA-Binding Proteins / genetics*


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