However, in a premutation individual, CGG length is only significantly correlated with the central executive, not with either phonological memory or visual–spatial memory. Fertility
About 20% of women who are carriers for the fragile X premutation are affected by fragile X-related primary ovarian insufficiency (FXPOI), which is defined as early menopause, which is menopause occurring before 40 ayears of age (average age at menopause is 51 years old in the US). The number of CGG repeats correlates with penetrance and age of onset, but it is not a linear relationship. However premature menopause is more common in premutation carriers than in women with the full mutation, and the highest risk for FXPOI is observed in women with between 70-100 repeats the risk of FXPOI. Fragile X-associated primary ovarian insufficiency (FXPOI) is one of three Fragile X-associated Disorders (FXD) caused by changes in the FMR1 gene. FXPOI affects female premutation carriers of which is caused by the FMR1 gene, when their ovaries are not functioning properly. Women with FXPOI may exhibit changes in menstrual cycles and have changes in hormone leves but not bec considered menopausal. Women with FXPOI still have the change get pregnant in some cases, about 10%, because their ovaries occasionally release viable eggs through "escape" ovulation.FMRP is a chromatin-binding protein that functions in the DNA damage response. FMRP also occupies sites on meiotic chromosomes and regulates the dynamics of the DNA damage response machinery during spermatogenesis.
The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5 untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA·DNA duplex.A subset of people with intellectual disability and symptoms resembling fragile X syndrome are found to have point mutations in FMR1. This subset lacked the CGG repeat expansion in FMR1 traditionally associated with fragile x syndrome. Inheritance
Fragile X syndrome has traditionally been considered an X-linked dominant condition with variable expressivity and possibly reduced penetrance. However, due to genetic anticipation and X-inactivation in females, the inheritance of Fragile X syndrome does not follow the usual pattern of X-linked dominant inheritance, and some scholars have suggested discontinuing labeling X-linked disorders as dominant or recessive. Females with full FMR1 mutations may have a milder phenotype than males due to variability in X-inactivation.Before the FMR1 gene was discovered, analysis of pedigrees showed the presence of male carriers who were asymptomatic, with their grandchildren affected by the condition at a higher rate than their siblings suggesting that genetic anticipation was occurring. This tendency for future generations to be affected at a higher frequency became known as the Sherman paradox after its description in 1985. Due to this, male children often have a greater degree of symptoms than their mothers.The explanation for this phenomenon is that male carriers pass on their premutation to all of their daughters, with the length of the FMR1 CGG repeat typically not increasing during meiosis, the cell division that is required to produce sperm.