Fragile X syndrome (or syndrome Martin Bell) is a human genetic disease caused by mutation of the FMR1 gene on the X chromosome, this mutation in a male over in 4000 and a female at 6000. About 1 in 256 women are carriers of Fragile-X and can transmit it to their children. About 1 in 800 males are carriers of Fragile-X; their daughters will, in turn, carry the gene. It accounts with Down syndrome primacy as the most common genetic cause of mental retardation.
Normally, the FMR1 gene contains between 6 and 53 repeats of CGG codon (repetition of trinucleotidi). In individuals suffering from Fragile X syndrome, the FMR1 allele has more than 230 repetizioni of this codon. This level of expansion causes the methylation of cytosine in the promoter of the FMR1 gene, thus silencing the expression of the FMR1 gene. The methylation of the locus FMR1, which is located on chromosome band Xq27.3, causing at that point, the constriction and the fragility of the X chromosome, a phenomenon that gives its name to the syndrome.
Males with a FMR1 gene with a significant expansion of the CGG triplet with the symptoms of the disease, since you normally have only one copy of chromosome X. Females, by contrast, have two copies of chromosome X and therefore have a chance to own at least twice a functional allele. The women with an expanded FMR1 gene on one of the two X chromosomes may show some symptoms of the disease or be normal (Figure right on all'ereditarietà linked recessive X chromosome does not correspond exactly to the case of Fragile X syndrome , But it exemplifies the situation).
Apart from the mental retardation of varying degrees from moderate to severe, other obvious features of the syndrome are elongated face, large ears, large testicles (macrorchidismo), and low muscle tone. Behavioral characteristics may include stereotypical movements (for example, beat their hands) and atypical social development, particularly shyness and limited eye contact situations. Some individuals suffering from Fragile X syndrome are also in the diagnostic criteria of autism.
The mutation and methylation of the FMR1 gene leads to the abolition of production of the protein for which the FMR1 gene encoding, that FMRP (fragile-X mental retardation protein). FMRP is a protein binding to RNA (RNA-binding protein) expressed mainly in the testicles and brain tissues most affected by the syndrome. FMRP RNA is associated with major messengers coding neural protein, and regulates some essential aspects, such as transportation along the dendriti to the synapses and the translation into proteins. In the absence of FMRP, many of the target RNA messengers of the protein are more deregulated and are translated into protein. There are also new molecular functions of protein, such as adjusting the stability of messenger RNA.
Although there is still no cure for the syndrome, there is hope that a better understanding of its causes may lead to new therapies. Currently, the syndrome can be treated through behavioral therapy, special education, and when necessary, treatment of physical abnormalities. We advise people who have relatives suffering from Fragile X syndrome to contact the geneticists to assess the probability of having sick children, and to know the seriousness of the problems that may have affected the descendants of the syndrome.
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