XE fragile syndrome ... (Fragile XE syndrome) - Gen AFF2
The fragile XE syndrome is a genetic process that affects thinking ability and cognitive function. Most affected individuals have mild intellectual disability. In some affected individuals, cognitive function is limited below average, but not low enough to be classified as an intellectual disability.
Learning disabilities are the most common sign of impaired cognitive function in people with fragile XE syndrome. Learning problems are probably due to communication problems and behavioral problems , including delayed speech, small writing skills, hyperactivity and short attention span. Some people with autism demonstrate behaviors such as hand flapping, repetitive behaviors, and extreme interest in a particular topic. Unlike some other forms of mental retardation, fragile XE syndrome cognitive function remains stable and does not diminish with age.
This process is due to mutations in the gene AFF2 (AF4 / FMR2 family member 2), located on the long arm of chromosome X (Xq28). This gene encodes a protein found in the nucleus of cells, but whose function is not well understood. Some studies suggest that acts as a transcription factor, meaning it binds to specific DNA regions and helps control the activity of other genes, although the identity of these genes is unknown. Other studies show that the protein can bind to specific regions of the mRNA which served as a genetic model for encoding proteins. It is believed that the protein AFF2 helps control the cutting process and alternative binding. A AFF2 region gene containing a particular DNA segment, known as a trinucleotide repeat CCG. In most people, the number of repetition of CCG varies from 4 to about 40.
Almost all cases of fragile XE syndrome occurs when the GCC trinucleotide repeat expands abnormally. In people with fragile XE syndrome, GCC segment is repeated more than 200 times, which makes this region of the gene is unstable. When expanded, this region is known as the fragile site FRAXE .. As a result, the gene is silenced AFF2 not encode protein and AFF2. It is unclear how the absence of this protein leads to intellectual disability in people with fragile XE syndrome. It is said that people with a repetition of 50 to 200 GCC have AFF2 premutation gene. It has been found that people with a premutation have no associated cognitive problems. Rarely, the FXS XE is associated with small deletions of genetic material AFF2 gene, although it is unknown how these deletions affect the protein and result in mental retardation.
Fragile XE syndrome is inherited as a dominant X - linked pattern in women who have two X chromosomes, a mutation in one of the two copies of the gene in each cell it is sufficient to express the disease. In males, who have only one X chromosome, a mutation in the single gene copy in each cell causes the disease. In most cases, men report more severe symptoms of the disease than women. In parents with AFF2 premutation gene, the number of repetitions can be increased CCG over 200 in reproductive cells. This means that parents with the permutation have an increased risk of having a child with Fragile XE. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. Children receive a Y chromosome from his father, which does not include the AFF2 gene.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with Fragile XE, by complete PCR amplification of exons AFF2 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).