Recent studies report a higher risk of dementia and motor symptoms in females with the fragile X mental retardation 1 premutation (PM-carriers) than has hitherto been appreciated.
Shorter telomeres (relative to age-matched controls) were observed in 5/5 individuals with FXTAS and dementia, in 2/2 individuals with FXTAS without dementia, and in 3/3 individuals with the fragile X premutation only (P values ranged from <0.001 to <0.05; Student's t-test), indicating that telomere shortening is associated with the premutation expansion of the FMR1 gene.
Because of the high prevalence of FMR1 premutation in the general population, the description and characterization of the FXTAS syndrome is of great interest as it may represent one of the more common monogenic causes of ataxia, tremor, and dementia.
Premutation alleles of the fragile X mental retardation 1 (FMR1) gene give rise to a late-onset movement disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by progressive intention tremor and gait ataxia, with associated dementia and global brain atrophy.