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

Edmund C. Jenkins, Flora Tassone, Lingling Ye, Hong Gu, Man Xi, Milen Velinov, W. Ted Brown, Randi J Hagerman, Paul J Hagerman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1543-1546
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Volume146
Issue number12
DOIs
StatePublished - Jun 15 2008

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Telomere
Intellectual Disability
Alleles
Dementia
Genes
Telomere Shortening
Down Syndrome
Dyskeratosis Congenita
T-Lymphocytes
Fragile X Tremor Ataxia Syndrome
Cell Aging
Alzheimer Disease
Biomarkers
Students

Keywords

  • Dementia
  • FMR1
  • FXTAS
  • Metaphase
  • Parkinson
  • Telomere shortening

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Reduced telomere length in older men with premutation alleles of the fragile X mental retardation 1 gene. / Jenkins, Edmund C.; Tassone, Flora; Ye, Lingling; Gu, Hong; Xi, Man; Velinov, Milen; Brown, W. Ted; Hagerman, Randi J; Hagerman, Paul J.

In: American Journal of Medical Genetics, Part A, Vol. 146, No. 12, 15.06.2008, p. 1543-1546.

Research output: Contribution to journalArticle

Jenkins, Edmund C. ; Tassone, Flora ; Ye, Lingling ; Gu, Hong ; Xi, Man ; Velinov, Milen ; Brown, W. Ted ; Hagerman, Randi J ; Hagerman, Paul J. / Reduced telomere length in older men with premutation alleles of the fragile X mental retardation 1 gene. In: American Journal of Medical Genetics, Part A. 2008 ; Vol. 146, No. 12. pp. 1543-1546.
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