Women who carry a fragile X premutation are biologically older than noncarriers as measured by telomere length

Am J Med Genet A. 2017 Nov;173(11):2985-2994. doi: 10.1002/ajmg.a.38476. Epub 2017 Sep 21.

Abstract

Women who carry a fragile X premutation, defined as having 55-200 unmethylated CGG repeats in the 5' UTR of the X-linked FMR1 gene, have a 20-fold increased risk for primary ovarian insufficiency (FXPOI). We tested the hypothesis that women with a premutation + FXPOI have shorter telomeres than those without FXPOI because they are "biologically older." Using linear regression, we found that women carrying a premutation (n = 172) have shorter telomeres and hence, are "biologically older" than women carrying the normal size allele (n = 81). Strikingly, despite having shorter telomeres, age was not statistically associated with their telomere length, in contrast to non-carrier controls. Further, telomere length within premutation carriers was not associated with repeat length but was associated with a diagnosis of FXPOI, although the latter finding may depend on FXPOI age of onset.

Keywords: FMR1; FXPOI; FXTAS; fragile X premutation; telomere length.

MeSH terms

  • 5' Untranslated Regions / genetics
  • Adult
  • Alleles
  • Cellular Senescence / genetics
  • DNA Methylation / genetics
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / epidemiology
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / physiopathology
  • Humans
  • Middle Aged
  • Mutation
  • Primary Ovarian Insufficiency / epidemiology
  • Primary Ovarian Insufficiency / genetics*
  • Primary Ovarian Insufficiency / physiopathology
  • Risk Factors
  • Telomere / genetics
  • Telomere Homeostasis / genetics*
  • Young Adult

Substances

  • 5' Untranslated Regions
  • FMR1 protein, human
  • Fragile X Mental Retardation Protein