The fragile X syndrome: implications of molecular genetics for the clinical syndrome

Eur J Clin Invest. 1994 Jan;24(1):1-10. doi: 10.1111/j.1365-2362.1994.tb02052.x.


The fragile X syndrome of mental retardation is one of the most common genetic diseases. Characterization of the mutations involved has greatly improved our knowledge of the transmission of fragile X syndrome and new DNA-based diagnostics tools significantly outperform cytogenetic testing both for establishing the diagnosis and for determining carrier status. Fragile X mutations consist of an expansion of a CGG trinucleotide repeat localized in a gene (FMR-1) that is abnormally methylated in all affected individuals. They are classified as premutations (asymptomatic) and full mutations (associated with the disease). Several different DNA analysis protocols are used for fragile X genotyping but only a few have been tested on large samples of individuals. There are several clinical indications for direct DNA genotyping for fragile X including mental retardation, learning disability or hyperactivity in children with or without a family history of mental retardation, the establishment of carrier diagnosis in fragile X families and prenatal screening of children from carrier women.

Publication types

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

MeSH terms

  • Child
  • DNA Mutational Analysis
  • Female
  • Fragile X Syndrome / diagnosis
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / prevention & control
  • Genetic Carrier Screening
  • Genotype
  • Humans
  • Male
  • Mass Screening
  • Molecular Biology
  • Oligodeoxyribonucleotides / genetics
  • Pedigree
  • Phenotype
  • Pregnancy
  • Prenatal Diagnosis
  • Repetitive Sequences, Nucleic Acid


  • Oligodeoxyribonucleotides