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A conservative news and views blog.

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Friday, September 02, 2005

The Fragile X

In my recent article on Darwin I mentioned Fragile X, which results from the disintegration of the end of one arm of the X chromosome . Fragile X is the leading inherited cause of mental retardation, and a great scourge, since it usually ends a family line. Believe me, I know.

A reader took umbrage with my description of Fragile X, and wrote a letter to the American Thinker, which Thomas Lifson graciously published. Read the letter in it`s entirety below:


Dear Editor,

As a parent of a child with Fragile X Syndrome, I wanted to clarify that Fragile X Syndrome is not a result of "chromosomal decay where one of the legs of the X has crumbled away" as described in the August 30th article by Tim Birdnow.

According to the National Fragile X Foundation Website: (www.fragilex.org)
A change or mutation in a gene on the X chromosome causes the fragile X syndrome. Chromosomes are packages of genes that are passed from generation to generation. Most individuals have 46 chromosomes, two of which are sex chromosomes. In females, these are two X's; in males they are and X and Y. Genes are given names to identify them and the gene responsible for fragile X syndrome is called the FMR1 (fragile X mental retardation 1) gene. The mutation is in the DNA (the chemical that makes up genes), of the X chromosome. The gene appears in three forms that are defined by the number of repeats of a pattern of DNA called CGG repeats. Individuals with less than 60 CGG repeats have a normal gene. Individuals with 60-200 CGG repeats have a premutation which means they carry an unstable mutation which can expand in future generations. Individuals with over 200 repeats have a full mutation which causes fragile X syndrome. The full mutation causes the gene to shut down or methylate a region of the FMR-1 gene. Normally, the FMR-1 gene produces an important protein called FMRP. When the gene is turned off, the individual does not make fragile X mental retardation protein (FMRP). The lack of this specific protein causes fragile X syndrome.

Mr. Birdnow suggested that the gene decays. That is not factual. While we always appreciate the fact that more people are learning about Fragile X Syndrome, it's important to be armed with factual information about the cause and symptoms of Fragile X Syndrome. I invite you to visit www.fragilex.org or www.fraxa.org for more information on Fragile X Syndrome.


Steve Strom

___________________________________________________
I responded:



I just wanted to clarify the point made by reader Steve Strom about Fragile X. He is correct in that Fragile X is caused by a mutation (which was my whole point) but what I said about Fragile X was correct. Obviously, I couldn`t go into a long dissertation about the FMR1 gene.

This is from the Pediatric Bulletin http://home.coqui.net/myrna/fragile.htm

``Fragile X syndrome is the most commonly inherited form of mental retardation. Although it is thought to be an X-linked recessive trait with variable expression and incomplete penetrance, 30% of all carrier women are also affected. The syndrome is called “fragile-X” because there exists a fragile site or gap at the end of the long arm of the X-chromosome in lymphocytes of affected patients when grown in a folate deficient medium.``

In short, one of the legs of the chromosome is crumbling away because of this mutation.

My wife has fragile X in her family, as well as two M.D.`s (both of whom have Fragile X children) who have explained this to me. Steve Strom is correct, but so am I.

Here http://www.ikm.jmu.edu/Buttsjl/ISAT493/Fragile%20X%20Syndrome/fragilexintro.html is a picture of the collapsing end of the x chromosome in a Fragile X carrier.

According to USA Today`s Health Encyclopedia:

Some people have chromosomes that when studied in a laboratory, have a tendency to "break" or "tear." The damage to these aberrant chromosomes typically occurs in particular regions, called fragile sites.

Also, Dr. Jennifer Jewell http://www.emedicine.com/PED/topic800.htm writes:


The genetic defect is dynamic and lies at the distal end of the long arm of the X chromosome. Careful examination of the karyotype of affected individuals' lymphocytes, cultured in a folate-depleted and thymidine-depleted medium, reveals a constriction followed by a thin strand of genetic material extending beyond the long arm at the highly conserved band Xq27.3. This constriction and thin strand produces the appearance of a fragile portion of the X chromosome, leading to the term fragile X. The function of the band Xq27.3, which is also termed the fragile X mental retardation (FMR1) gene, is currently unclear but is believed to play a role in normal brain development. Once identified and sequenced, the gene was discovered to contain a repeating base pair triplet (CGG) expansion, which is responsible for fragile X syndrome.

In other words, the end of one arm of the X chromosome is collapsing, with a strand of molecules trailing off.

That this collapse is caused by a genetic mutation does not invalidate my point. My point was that genes, and chromosomes, mutate in non-beneficial ways, and that the idea that random mutations evolve an organism for the better is dubious. Also, Mr.
Strom states that Fragile X is caused by genetic mutation, then says it is not from genetic disintigration. What exactly IS genetic mutation other than a form of disintigration?
___________________________________________________


My point in the article, of course, was that a slight change to one gene causes a structural defect at the tip of a chromosome, and this ``hanging chad`` causes enormous problems for the inheritor. That genes and chromosome mutate is without question, and those mutations are unavoidable and inevitably harmful. We all suffer from genetic drift as we age, which is probably why our sex drive begins to shut down and a woman passes her childbearing years. Still, why hasn`t this drift corrupted the gene pool? Men can father children into old age (I believe Charlie Chaplin was in his 90`s when he fathered a child.) These mutations should corrupt the gene pool, not drive it upwards. The idea that mutations lead to evolution is hard to swallow; things wind down.


Getting back to Fragile X; people often ask my wife and me why we don`t have children. This is one of the primary reasons; my wife has the premutation, and we will probably be passing along the SYNDROME to any children we would conceive. She has four syblings, and all but one have Fragile X children. Fragile X ends families.

My wife`s sister is an M.D., and so is her other sister`s husband, and they are both active in the cause, as is the rest of her family. Their children have a range of problems; hyperactivity, emotional problems, slow cognitive developement, epilepsy, etc. Fortunately, only one boy is affected (Fragile X is generally much worse in boys), and the girls range from fairly minor to moderately severe.

Great strides are being made towards developing gene therapy and other therapies to treat Fragile X Syndrome. Like all genetic disorders, it is going to be a long and laborious process, and actually CURING the disorder is not likely in the forseeable future. Still, early intervention may help prevent the Syndrome from developing and ruining lives.


(Apologies to Furniture Cat who left a message while I was trying to repair formatting problems with this post. I have lost her comments in the process; please feel free to write back to me!)

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3 Comments:

Blogger TJ Willms said...

You are right again Tim,


Your explanation of the “Fragile X syndrome” here is as clear and concise as was your article on the over-reaching philosophy of Darwinian practitioners. I have to agree with your editorial decision to not go into great depth on this issue there; it would have badly bogged down the previous article. The reader would have lost touch with the focus of the piece and your point would have been overwhelmed in the minutia of describing this single aspect. I will also say that you have addressed any lack of detail in the earlier piece very well and thoroughly here.

Not all genetic mutations will ever produce a completely beneficial result. Just look at any of the endeavors involving animal husbandry and you will see evidence of this. Dogs as a prime example will often exhibit undesirable behavioral characteristics even though they have been bred to achieve the perfect standard of their respective breeds. The only manifestation of selective reproduction in humans comes when they make an informed decision not to have children such as you and your wife have. Therefore, most genetic mutations in humans only come to our attention when something goes wrong.

So, ambling further down that line of thought the progenitor of the next step in human “evolution,” could "theoretically" already be out there we simply wouldn’t be aware of it because it wouldn’t diagnosed as any kind of problem.

I think?

3:21 PM  
Blogger John said...

Absolutely incredible stuff, way over my head. Great job.

3:47 PM  
Anonymous Anonymous said...

http://pharyngula.org/index/weblog/comments/timothy_birdnow

12:11 PM  

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