SNP Shot: Genomic Insights

Fragile X-associated primary ovarian insufficiency (FXPOI) is a condition affecting women that impairs ovarian function. The ovaries, responsible for egg production, experience reduced activity. As a type of primary ovarian insufficiency, FXPOI can lead to inconsistent periods, premature menopause, infertility, and increased follicle-stimulating hormone (FSH) levels. FSH, present in both sexes, regulates reproductive cell development (eggs in women and sperm in men). In women, FSH levels fluctuate but generally increase with age. Elevated FSH in younger women can signal early menopause and fertility issues.

The impact of FXPOI varies. Women with the most severe form experience overt POI (previously premature ovarian failure), characterized by irregular or absent menstruation and high FSH levels before age 40, frequently causing infertility. Others have occult POI, marked by normal periods but decreased fertility, possibly accompanied by elevated FSH (biochemical POI). The decreased ovarian function in FXPOI leads to low estrogen levels, triggering menopausal symptoms like hot flashes, insomnia, and osteoporosis. On average, women with FXPOI experience menopause five years sooner than those without the condition.

Inheritance:

The increased likelihood of developing FXPOI is inherited in an X-linked dominant manner. The FMR1 gene, located on the X chromosome (one of the two sex chromosomes; the other being the Y chromosome), is involved. The inheritance is dominant because only one copy of the altered gene per cell is enough to increase the risk of FXPOI. In females (possessing two X chromosomes), a mutation in one of their gene copies can lead to the disorder. However, not every woman inheriting an FMR1 premutation will develop FXPOI. Since males lack ovaries, they are not affected by FXPOI.