FMR1 premutation is an uncommon explanation for premature ovarian failure in Han Chinese

PLoS One. 2014 Jul 22;9(7):e103316. doi: 10.1371/journal.pone.0103316. eCollection 2014.


Background: In premature ovarian failure (POF), cessation of menstruation occurs before the expected age of menopause. Approximately 1% of women are affected. FMR1 premutation was reported to be responsible for up to 3.3%-6.7% of sporadic POF and 13% of familial cases in Caucasians, while the data was absent in Chinese population. Therefore, the impact of FMR1 CGG repeat on ovarian reserve is needed to be investigated in large Chinese cohort.

Methods: The number of FMR1 CGG repeat was determined in 379 Han Chinese women with well-defined 46, XX non-syndromic sporadic POF and 402 controls. The age of menopause onset in respect to CGG repeats was further analyzed.

Results: The frequency of FMR1 premutation in Han Chinese POF was only 0.5% (2/379), although it was higher than that in matched controls (0%, 0/402), it was much lower than that reported in Caucasian with POF (3.3%-6.7%). The prevalence of intermediate FMR1 (41-54) was not increased significantly in sporadic POF than that in controls (2.9% vs. 1.7%, P = 0.343). However, POF patients more often carried a single additional CGG repeat in a single allele than did fertile women (allele-1: 29.7 vs. 28.8, P<0.001; allele-2: 32.6 vs. 31.5, P < 0.001). POF patients with both alleles of CGG repeats outside (below or above) the normal range (26-34) showed an earlier age of cessation of menses than those with two alleles within normal range (hom-high/high vs. norm: 20.4 ± 4.8 vs. 24.7 ± 6.4, p < 0.01; hom-low/high vs. norm: 18.7 ± 1.7 vs. 24.7 ± 6.4, p < 0.01).

Conclusions: FMR1 premutation seems to be an uncommon explanation for POF in Han Chinese. However, having both alleles with CGG repeats outside the normal range might still adversely affect ovarian aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging
  • Alleles
  • Asian Continental Ancestry Group / genetics
  • China / epidemiology
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Genotype
  • Humans
  • Menopause / genetics
  • Ovary / metabolism
  • Ovary / pathology
  • Primary Ovarian Insufficiency / epidemiology*
  • Primary Ovarian Insufficiency / genetics
  • Primary Ovarian Insufficiency / pathology
  • Trinucleotide Repeats


  • FMR1 protein, human
  • Fragile X Mental Retardation Protein

Grant support

This work was supported by the National Basic Research Program of China (973 program-2012CB944700); the National Natural Science Foundation of China (81270662); Foundation for the Author of National Excellent Doctoral Dissertation of China (201078); and Independent Innovation Foundation of Shandong University, IIFSDU (2012TS130). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.