Unexpected inheritance of the (CGG)n trinucleotide expansion in a fragile X syndrome family

Eur J Hum Genet. 1996;4(1):8-12. doi: 10.1159/000472163.

Abstract

The fragile X syndrome is the most frequent cause of inherited mental retardation. CGG repeat alleles are usually classified as normal, premutation, or full mutation based on the length of this triplet in the 5' untranslated region of the FMR1 gene. The pattern of inheritance follows a two-stage intergenerational process in which the premutation evolves into the full mutation. Some reverse mutations have been described, but they appear to be very rare. We describe a family in which a mother of two affected males herself carried a full mutation. Surprisingly, her clinically normal daughter, initially considered to be a carrier by linkage analysis, carried a very short premutation. Findings from our family study corroborate the hypothesis that the expansion during female transmission could be a postzygotic event and raise the problem of mosaicism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Southern
  • DNA Probes
  • Female
  • Fragile X Syndrome / diagnosis
  • Fragile X Syndrome / genetics*
  • Genetic Linkage
  • Humans
  • Male
  • Mutation
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Prenatal Diagnosis
  • Trinucleotide Repeats / genetics*
  • X Chromosome / genetics

Substances

  • DNA Probes