Screening for FXTAS in 95 Spanish patients negative for Huntington disease

Genet Test. 2008 Mar;12(1):135-8. doi: 10.1089/gte.2007.0074.

Abstract

Fragile X syndrome is the most common form of hereditary mental retardation. The molecular basis of this syndrome is mainly a CGG expansion in the 5' untranslated region of the FMR1 gene. Expansions with more than 200 CGG repeats abolish gene expression causing the classical fragile X phenotype. Premutation carriers (55-200 CGG) have normal cognitive function with increased risk of developing premature ovarian failure and fragile X-associated tremor-ataxia syndrome (FXTAS). Some clinical features associated with FXTAS, such as tremor, gait ataxia, cognitive decline, and generalized brain atrophy, are also seen in other movement disorders. Ninety-five patients referred for HD, who tested negative for the expansion in the IT15 gene, were screened for FMR1 CGG-repeat expansion. One FMR1 premutation male carrier was detected, giving an FXTAS frequency of 1.6%. Our results highlight that FXTAS is still not well diagnosed; therefore, we recommend FMR1 premutation screenings in all patients with late-onset tremor, ataxia, and cognitive dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Aged
  • Ataxia / genetics
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / diagnosis*
  • Fragile X Syndrome / genetics*
  • Genetic Testing
  • Heterozygote
  • Humans
  • Huntingtin Protein
  • Huntington Disease / diagnosis*
  • Huntington Disease / genetics*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Phenotype
  • Spanien
  • Tremor / genetics
  • Trinucleotide Repeat Expansion

Substances

  • 5' Untranslated Regions
  • FMR1 protein, human
  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Fragile X Mental Retardation Protein