Fragile X syndrome and Fragile X-Associated Diminished Ovarian Reserve

Fragile X syndrome (FXS) (OMIM #300624) is the most common cause of heritable intellectual disability and is the leading single-gene defect associated with autism, affecting approximately 1:4,000 males and 1:8,000 females. FXS is caused by a CGG repeat expansion in the 5′UTR of the fragile X mental retardation (FMR1) gene on the X chromosome. Besides FXS, expansion of CGG repeats within the FMR1 gene is also associated with other disorders: fragile X–associated primary ovarian insufficiency (FXPOI)and fragile X–associated tremor ataxia syndrome.Whereas FXS is caused by CGG repeat length of over 200 (full mutation (FM)) and FMR1 gene silencing, it has been proposed that FXPOI and fragile X–associated tremor ataxia syndrome are caused by toxic FMR1 messenger RNA (mRNA) and/or expression of an aberrant FMRpolyG protein in premutation (PM) patients with 55–200 repeats.