Primary ovarian failure associated with fragile X (Fragile X-associated primary ovarian insufficiency) - FMR1 gene            

Primary ovarian failure associated with fragile X (FXPOI) is a disease that affects only women and is characterized by decreased ovarian function. As a form of primary ovarian failure, FXPOI can lead to irregular menstrual cycles, early menopause, infertility and high concentrations of follicle stimulating hormone (FSH). FSH is produced in both men and women and helps regulate cell development. In women, FSH concentrations increase and decrease but generally increases as women age. In young women, high concentrations can lead to early menopause and fertility problems.

FXPOI severity varies. Women are affected more primary ovarian failure (POI), formerly POF. These women have irregular or absent menstrual periods and high concentrations of FSH before 40 years of age. Other women have POI hidden, characterized by normal menstrual periods, reduced fertility, and high concentrations of FSH, in which case it is called POI biochemistry. Reduction of ovarian function caused by FXPOI results in low levels of estrogen, which leads to many of the signs and symptoms of menopause, such as hot flashes, insomnia and osteoporosis. FXPOI women have menopause an average of 5 years earlier than women without the disease.

It has been shown that mutations in FMR1 (Fragile X Mental Retardation 1), located on the long arm of the X (Xq27.3) chromosome, increase the risk of developing FXPOI. This gene encodes FMRP, which is present in many tissues, including the brain, testes and ovaries. In the brain, it can play a role in the development of the synapse, where communication from cell to cell occurs. Specifically, FMRP may help regulate synaptic plasticity, which is important for learning and memory. The role of protein in testes and ovaries not well understood. Also has binding capacity to certain mRNAs and participate in traffic mRNA from the nucleus to the cytoplasm. A region of the FMR1 gene trinucleotide repeat containing CGG. In most people, the number of CGG repeats ranges from below 10 to about 40. This segment repeat CGG usually interrupted several times by a sequence of three different bases, AGG. Having AGG between CGG triplet seems to help stabilize the long repeat segment.

An expansion of trinucleotide repeats in FMR1 increases the risk of developing primary ovarian failure associated with fragile X (FXPOI) in women. In this situation, the CGG trinucleotide repeat in FMR1 is repeated about 55 to 200 times, which is known as a premutation. About 20% of women with a permutation have the most severe form of the disease, called primary ovarian insufficiency (POI), which leads to abnormal menstrual cycles, high concentrations of FSH before 40 years of age and often , infertility. Other women with POI have hidden permutation, a milder form of the disease that leads to reduced fertility, although women have normal menstrual cycles. For unknown reasons, the premutation leads to overproduction of mRNA in FMR1 containing repeat expansion. It is believed that the abnormal mRNA is responsible for the signs and symptoms of FXPOI. It is thought that the mRNA binds to other proteins and inhibit their functions. In addition, repetitions impede protein synthesis, and therefore, some people with premutation FMR1 gene have lower protein FMRP. As a result, they may have mild versions of the physical features seen in fragile X syndrome, such as prominent ears, and emotional problems such as anxiety or depression.

An increased risk of developing FXPOI is inherited as a dominant X - linked pattern The FMR1 gene is on the X chromosome, one of the two sex chromosomes. Inheritance is dominant because a copy of the altered gene in each cell is sufficient to raise the risk of developing FXPOI. In females, having two X chromosomes, a mutation in one of the two copies of the gene in each cell may express the disease. However, not all women who inherit a FMR1 premutation develop FXPOI.

Tests in IVAMI: in IVAMI perform detection of mutations associated with primary ovarian failure associated with fragile X (FXPOI), by complete PCR amplification of the exons of the FMR1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).

ra separation of white blood cells, or impregnated card with dried blood sample (IVAMI can mail the card to deposit the blood sample).