Evidence for, and a spectrum of, neurological involvement in carriers of the fragile X pre-mutation: FXTAS and beyond

Danuta Z. Loesch, A. Churchyard, P. Brotchie, M. Marot, Flora Tassone

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


A neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), occurs in some older men carrying a small CGG repeat expansion (pre-mutation) in the FMR1 gene. We surveyed a sample of older pre-mutation males to estimate the prevalence and spectrum of neurological involvement. Twelve pre-mutation males aged 50-82 years and 11 age-matched normal controls ascertained in an unbiased manner were included in a neurological assessment that also used standard scales for tremor (Clinical Rating Scale for Tremor), ataxia (International Cooperative Ataxia Rating Scale, ICARS) and parkinsonian signs (Unified Parkinson's Disease Rating Scale). Axial FLAIR images of the brain, and neuropsychological and molecular tests were also conducted in pre-mutation carriers. The neurological disorder meeting all the criteria for diagnosis of 'definite' to 'possible' FXTAS occurred in five of 12 pre-mutation carriers (41.7%), and this prevalence was significantly higher compared with normal controls (0%). The ataxia (ICARS) score and the sum of all three tremor/ataxia scores were significantly higher in pre-mutation carriers than in controls, and mRNA was elevated in all but one carrier, but did not correlate with the degree of neurological involvement. In conclusion, the findings provide further evidence that the pre-mutation allele of FMR1 is a significant cause of late-onset neurodegeneration, presenting with a broad spectrum of clinical manifestations.

Original languageEnglish (US)
Pages (from-to)412-417
Number of pages6
JournalClinical Genetics
Issue number5
StatePublished - May 2005


  • Fragile X
  • Magnetic resonance imagining
  • Pre-mutation
  • Prevalence
  • Tremor score
  • Tremor/ataxia

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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