Syndrome, Fragile

Trinucleotide sequences that increase in number (microsateUite instability) can cause disease. The unstable p(CGG) repeat sequence is associated with the fragile X syndrome. Other trinucleotide repeats that undergo dynamic mutation (usually an increase) are associated with Huntington s chorea (CAG), myotonic dystrophy (CTG), spinobulbar muscular atrophy (CAG), and Kennedy s disease (CAG). 

Vanderklish, P. W., and Edelman, G. M. (2005). Differential translation and fragile X syndrome. Genes Brain Behav. 4, 360-384. 

Finally, this section has focused almost entirely on axonal transport, but dendritic transport also occurs [25]. Since dendrites usually include postsynaptic regions while most axons terminate in presynaptic elements, the dendritic and axonal transport each receive a number of unique proteins. An added level of complexity for intraneuronal transport phenomena is the intriguing observation that mRNA is routed into dendrites where it is implicated in local protein synthesis at postsynaptic sites, but ribosomal components and mRNA are largely excluded from axonal domains [26]. Regulation of protein synthesis in dendritic compartments is an important mechanism is synaptic plasticity [27,28]. The importance of dendritic mRNA transport and local protein synthesis is underscored by the demonstration that the mutation associated with Fragile X syndrome affects a protein important for transport and localization of mRNA in dendrites [27, 29], Similar processes of mRNA transport have been described in glial cells [30]. 

Gibson, T. J., Rice, P. M., Thompson, J. D., and Heringa, J. (1993). KH domains within the FMR1 sequence suggest that Fragile-X syndrome stems from a defect in RNA metabolism. Trends Biochem. Sci. 18, 331-333. 

The signs and symptoms of some genetic conditions tend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next. This phenomenon is called anticipation. Anticipation is most often seen with certain genetic disorders of the nervous system, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. 

Trinucleotide Repeat Expansion DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats, [nih]... 

Ehlers-Danlos syndromes Mutations in collagen genes and lysine hydroxylase gene Hyperextensible, fragile skin HypermobUe joints, dislocations, varicose veins, ecchymoses, arterial, intestinal ruptures... 

A 6-year-old boy has a family history of mental retardation and has developmental delay and some unusual facial features. He is being evaluated for possible Fragile X syndrome. Which of the following would be most useM in helping to establish the diagnosis ... 

Answer A. The presence of an expanded trinucleotide repeat in 5 untranslated region of the gene is an accurate test for fragile X syndrome. 

An IQ test (choice B) would be useful because the IQ is typically much lower than average in Fragile X syndrome patients. However, many other syndromes also include mental retardation as a feature, so this would not be a specific test. 

Testicular volume (choice E) is increased in males with fragile X syndrome, but this is observed in postpubertal males. 

This is normal and usually causes no problem. However, in some cases, the triplet repeat segment of the gene is expanded. This growth may increase in successive generations of families. If the triplet repeat number becomes too great, disease can result. Here are two specific examples, Huntington s disease and Fragile X syndrome. 

Fragile X syndrome has some things in common with Hnntington s disease. The genetic defect is in the FMRl (Fragile X mental retardation 1) gene. The affected protein is FMRP (Fragile X mental retardation protein). 

Fragile X syndrome is the leading inherited cause of mental retardation in humans. It affects about 1 out of 2000 males and about 1 out of 4000 females. The degree of mental retardation is quite variable, from a mild mental impairment to severe mental retardation. The disease is frequently more serious in males than females males have only the defective X chromosome, whereas females have one normal X chromosome to go along with the defective one. There is no specific treatment for Fragile X syndrome. 

Biacsi, R., Kumari, D. and Usdin, K. (2008) SIRTl inhibition alleviates gene silencing in Fragile X mental retardation syndrome. PLoS Genetics, 4, el000017. 

Fragile X syndrome is the most common inherited form of mental retardation, with a freguency of i in 4000 males and I in 8000 females. 

Symptoms of Fragile X syndrome include cognitive impairment, autism, seizures, and hyperactivity. 

---