Rare variants in the promoter of the fragile X syndrome gene (FMR1)

M. Milà, S. Castellví-Bel, A. Sánchez, A. Barceló, C. Badenas, J. Mallolas, Xavier P. Estivill

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Fragile X syndrome, the most common form of familial mental retardation, is mainly caused by the expansion of an unstable region of CGG repeats in the 5' untranslated region of the FMR1 (Fragile X Mental Retardation-1) gene. Molecular tools to detect an abnormal CGG expansion in FMR1 include Southern blot hybridization and PCR amplification. Southern blotting with the StB12.3 probe and EcoRI/EagI double digestion is widely used as a routine test for fragile X syndrome diagnosis in laboratories around the world. A patient with mental retardation of unknown origin showed absence of digestion for EagI due to a -149C→G substitution in the CpG island of the FMR1 gene, which destroys that restriction enzyme site. Screening for other changes around that region also detected a -154insGGC in a patient with a phenotype highly suggestive of fragile X syndrome but without CGG expansion. Expression studies did not show any abnormal changes in FMR1 function. In summary, we have identified two different changes (a C to G substitution at -149 and a GGC insertion at -154) in the promoter of the FMR1 gene. These are the first variants described in the promoter of the FMR1 gene. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)115-119
Number of pages5
JournalMolecular and Cellular Probes
Issue number2
Publication statusPublished - Apr 2000
Externally publishedYes



  • DNA variant
  • FMR1 gene
  • Fragile X syndrome
  • Promoter region

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Milà, M., Castellví-Bel, S., Sánchez, A., Barceló, A., Badenas, C., Mallolas, J., & Estivill, X. P. (2000). Rare variants in the promoter of the fragile X syndrome gene (FMR1). Molecular and Cellular Probes, 14(2), 115-119. https://doi.org/10.1006/mcpr.2000.0293