Fragile X-associated primary ovarian insufficiency
| Fragile X-associated primary ovarian insufficiency | |
|---|---|
| Other names | premature ovarian failure |
| Pronunciation |
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| Specialty | Genetics, reproductive endocrinology |
| Symptoms | Elevated follicle stimulating hormone (FSH) and loss of menstrual cycles before age 40 |
| Causes | FMR1 premutation |
| Diagnostic method | genetic testing |
| Treatment | infertility: may use assisted reproductive technologies risk of FMR1 premutation expansion: genetic testing for CGG repeat expansion in embryos or fetuses |
Fragile X-associated primary ovarian insufficiency (FXPOI) is the most common genetic cause of premature ovarian failure in women with a normal karyotype 46, XX. The expansion of a CGG repeat in the 5' untranslated region of the FMR1 gene from the normal range of 5-45 repeats to the premutation range of 55-199 CGGs leads to risk of FXPOI for ovary-bearing individuals. About 1:150-1:200 women in the US population carry a premutation. Women who carry an FMR1 premutation have a roughly 20% risk of being diagnosed with FXPOI, compared to 1% for the general population, and an 8-15% risk of developing the neurogenerative tremor/ataxia disorder (FXTAS). FMR1 premutation women are also at increased risk of having a child with a CGG repeat that is expanded to >200 repeats (a full mutation). Individuals with a full mutation, unlike the premutation, produce little to no mRNA or protein from the FMR1 gene and have fragile X syndrome as a result.