Reduced telomere length in older men with premutation alleles of the fragile X mental retardation 1 gene

Topic: Brain proteins, microglia and lab models

Reduced telomere length has recently been reported in T lymphocytes of individuals with trisomy 21 Down syndrome (DS) and dementia. Shorter telomeres also have been documented in dyskeratosis congenita, cell senescence, Alzheimer disease, and neoplastic transformation. These observations suggest that similar shortening may occur in people with fragile X-associated tremor/ataxia syndrome (FXTAS), which frequently is accompanied by dementia. To test this hypothesis, telomere length has been quantified in T lymphocytes from older male carriers of premutation FMR1 alleles, with or without FXTAS, and FXTAS with dementia. 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. The current study design allowed simultaneous comparisons among control, premutation, FXTAS, and FXTAS with dementia samples, and showed nearly equal degrees of shortening relative to controls among the three premutation sample groups. Thus, telomere shortening may serve as a biomarker for cellular dysregulation that may precede the development of the symptoms of FXTAS.

Key findings

• These observations suggest that similar shortening may occur in people with fragile X-associated tremor/ataxia syndrome (FXTAS), which frequently is accompanied by dementia.
• 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.

Why it matters

This study found shorter telomeres in T lymphocytes from older men with fragile X premutation alleles, including those with fragile X-associated tremor/ataxia syndrome and dementia. It suggests telomere shortening may be a biomarker, but it is a small study and does not show a treatment or cure for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1002/ajmg.a.32342
• PubMed: 18478592
• Original source →
• Free full text: PubMed Central →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{jenkins2008-18478592,
  author  = {Jenkins, E. C. and Tassone, F. and Ye, L. and Gu, H. and Xi, M. and Velinov, M. and Brown, W. T. and Hagerman, R. J. and others},
  title   = {{Reduced telomere length in older men with premutation alleles of the fragile X mental retardation 1 gene}},
  journal = {American journal of medical genetics. Part A},
  year    = {2008},
  doi     = {10.1002/ajmg.a.32342},
  pmid    = {18478592},
  url     = {https://doi.org/10.1002/ajmg.a.32342}
}

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