What is fragile x syndrome?
The fragile X syndrome is a genetic disorder associated with mental retardation, autism-like behavior and often certain physical characteristics. The syndrome is caused by a mutation in a gene (FMR1) which is located on the X-chromosome. About 1 in 1,500 males and 1 in 2,500 women have this syndrome; that in the Netherlands about 2300 people every year 20 boys and 15 girls born with fragile X syndrome. This makes it, in the following Down syndrome, the most common genetic cause of mental retardation.
History and name
In 1943 Martin and Bell described a family with a sex-linked (ie, the condition affects mainly boys) inherited form of mental retardation. Later, it could be shown, that this family suffered from the fragile-X syndrome. In 1969 it was discovered that this syndrome was associated with a peculiarity of the X chromosome. When cells are cultured (e.g., from blood or skin) of patients with Fragile X Syndrome in a nutrient medium with low folic acid, occurs in the X-chromosome of a portion of the cultured cells of a break at the end of the long arm . So here is a "fragile site" a vulnerability, which the syndrome its name. In 1991, one finally discovered the FMR1gen which is located on that spot, and the deviation that causes the syndrome.
What causes fragile x syndrome?
The fragile X syndrome is caused by a change, mutation in the FMR1 gene, which is located on the X chromosome in band q 27.3, which is almost at the end of the long arm. The DNA of this gene codes for a portion of the FMRP protein, which plays an important role in the brains. Indicates DNA that code by means of the sequence of four chemical substances, A, G, C and T, which act as letters in an alphabet. Sets of three-letter code, each time for a particular amino acid, one of the building blocks of a protein, which is thus constructed according to the code of the DNA. When the fragile-X syndrome, there is a change (mutation) formed in the DNA of the FMR1 gene; The "letter" CGG copied endlessly and is more than 230 times in a row for (more than 230 "repeats"). As a result, the gene can no longer function and acts on the disorder. The normal gene contains between 6 and 55 "CGG -repeats". When there is between the 50 and the 200 "CGG-repeats" are (an "premutation"), the gene can still function, but as the number of repeats in the formation of increasing the egg cell, the mutation is transmitted and enters the syndrome in the next generation on. When the FMR1 gene is not functioning, there will be a shortage of the FMR1-protein, the protein for which it encodes. The absence of this protein seems to lead to nerve cells react strongly to certain transmitters, particularly glutamate. This will relate to the dendritisiche spurs are abnormal in the fragile X syndrome.
Heredity
Women have two X chromosomes in every cell, males only one (and a Y chromosome). Among women in most cells one of the two X chromosomes made inactive. As a result, in the half of the cells a "healthy" X-chromosome active. Women with fragile X thus generally have a much less severe disabilities than men and can often be a healthy carrier. Men can the damaged X chromosome only inherit from their mother (their father they inherit the Y chromosome). The pattern of healthy carriers, which have affected children, called "gender" or "X-linked" inheritance. However, the scheme from the one pictured here is not entirely because many carriers of fragile X or disabled. A premutation is not associated with an intellectual disability and generations can be present in a family without going into a mutation. The transition to a mutation of more than 230 repeats occurs only with transmission by a woman, who then himself so no symptoms at all.
Fragile x syndrome symptoms
- Abnormalities in the face (relatively long face, large ears, prominent chin).
- Macro-orchidie (too large testes)
- Mild to severe mental disabilities; (in women usually mild, with men usually severe).
- Shy behavior, avoiding eye contact; This is called autistic.
- Flapping hands in excitement or stress;
- Language and speech disorders; For example, fast talking, often repeating the '' own '' words, sometimes incoherent talk.
- Cover Affordability of limbs; low muscle tone.
- ADHD-like behaviors among men with fragile X often;
- In women sometimes come to depression.
Diagnosis
The diagnosis of fragile X syndrome is suspected in people with intellectual disabilities and characteristics. But even if the typical features are lacking, will men or boys with intellectual disabilities, whose cause is unknown, though be deployed quickly investigate the fragile X syndrome. In the DNA of the lymphocytes from a blood sample looks at the extension of the gene that occurs when the number of repeats is increased. Can thus be determined whether the mutation is present. This research may also take place in amniotic fluid or placental villi.