Fragile X Syndrome

In my quest to find a rare genetic disease in the wonderful land of www-dot-coms, a rather annoying popup protruded my view of the Google search. At first, what I thought I saw was a furniture advertisement. At second glance, it appeared to be some type of "Wanna see my web cam". But, just as I clicked on the small, conveniently placed "X" in the corner of the window, I saw them. The words "rare genetic disease" and Fragile X were strewn all over the porthole, which lead into a dreamland of information. A click away and I was on my way into Ms. Frizzle of the Magic School Bus's classroom, just waiting to be educated. (Of course, there are no Magic School Bus books written about Fragile X, my newfound rare genetic disease friend.)

Fragile X syndrome affects one in four thousand males, and one in every eight thousand females around the globe. Its features include learning disability of varying severity, and behavioral problems such as hyperactivity and autistic tendencies. Fragile X's physical characteristics include a long face, protruding ears, lax joints, and in males: enlarged testes. There is no cure, but there is some evidence that treatment of the associated behavioral and educational problems can be beneficial.

Fragile X syndrome is caused by a mutation of the FMR-1 gene on the X chromosome (hence, fragile X"). Its connection to the X chromosome makes it sex-linked. The FMR-1 gene contains a sequence that consists of a variable number of repeats of the trinucleotide CGG, (representing cytosine and guanine). The sequence occurs in a part of the gene that is translated but not transcribed during protein synthesis. In a normal human, the number of CGG repeats varies between 5 and about 50. For members with Fragile X, the repeats last past 200, a condition known as a Full Mutation (known as FM). The full mutation prevents transcription of the FMR-1 gene, so that none of its protein product is made. Males have only one X chromosome, so if they carry a FM they are always affected. Females have two X chromosomes and the result of a FM in one chromosome can be very capricious: about 50% of such females show some symptoms of the syndrome and 20% are severely affected.

The unaffected mothers of fragile X individuals are consistently found to have an FMR-1 gene containing between 50 and 199 CGG repeats; this intermediary number is known as a premutation (PM). The population frequency of