The FMR1 premutation and reproduction

Michael D. Wittenberger, Randi J Hagerman, Stephanie L. Sherman, Allyn McConkie-Rosell, Corrine K. Welt, Robert W. Rebar, Emily C. Corrigan, Joe Leigh Simpson, Lawrence M. Nelson

Research output: Contribution to journalArticlepeer-review

292 Scopus citations


Objective: To update clinicians on the reproductive implications of premutations in FMR1 (fragile X mental retardation 1). Fragile X syndrome, a cause of mental retardation and autism, is due to a full mutation (>200 CGG repeats). Initially, individuals who carried the premutation (defined as more than 55 but less than 200 CGG repeats) were not considered at risk for any clinical disorders. It is now recognized that this was incorrect, specifically with respect to female reproduction. Design and Setting: Literature review and consensus building at two multidisciplinary scientific workshops. Conclusion(s): Convincing evidence now relates the FMR1 premutation to altered ovarian function and loss of fertility. An FMR1 mRNA gain-of-function toxicity may underlie this altered ovarian function. There are major gaps in knowledge regarding the natural history of the altered ovarian function in women who carry the FMR1 premutation, making counseling about reproductive plans a challenge. Women with premature ovarian failure are at increased risk of having an FMR1 premutation and should be informed of the availability of fragile X testing. Specialists in reproductive medicine can provide a supportive environment in which to explain the implications of FMR1 premutation testing, facilitate access to testing, and make appropriate referral to genetic counselors.

Original languageEnglish (US)
Pages (from-to)456-465
Number of pages10
JournalFertility and Sterility
Issue number3
StatePublished - Mar 2007


  • diminished ovarian reserve
  • FMR1
  • Fragile X syndrome
  • fragile X-associated tremor/ataxia syndrome
  • genetic counseling
  • hypergonadotropic amenorrhea
  • hypergonadotropic hypogonadism
  • low response to gonadotropin stimulation
  • premature menopause
  • premutation
  • primary hypogonadism
  • primary ovarian insufficiency
  • spontaneous premature ovarian failure

ASJC Scopus subject areas

  • Obstetrics and Gynecology


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