Tuesday, December 15, 2009

It was a coin flip …

And, I lost.

Spinal Bulbar Muscular Atrophy, aka Kennedy's Disease, is an X-linked disorder. In other words, an X-chromosome is defective (mutated). Kennedy's Disease is caused by a trinucleotide repeat expansion in the androgen receptor gene. This means that the cytosine-adenine-guanine (or CAG) that are normally repeated 1036 times mutate (expand in our DNA
string) to produce a larger repeat size of approximately 4062.

This CAG sequence is unstable and can change from one generation to the next leading to further expansions. If the person with the defective gene is the father, he cannot pass the gene on to any sons. However, he will pass the defective gene on to all the daughters. If the person with the defective gene is the mother, she is a carrier. With a carrier, there is a 50% chance that the defective gene will be passed to any of the offspring.

Often, there is a misconception that 50% means half of the offspring will have the defective gene. 50% = one out of two chances, right? No, it does not work that way. As with any coin flip, heads could come up five, six, or seven times in a row, for example, before a tails comes up. Alternatively, tails could come up several times before a heads finally comes up. The 50% means nothing more than over a very large number of flips, half of the time it will be heads.

My mother was a carrier. Either her mother or father passed along the defective X-chromosome to her. We do not have any family medical history that would help us determine whether it was her father or mother that had the defective gene. My mother gave birth to ten children (3 girls and 7 boys). If the 50% rule worked exactly, five of the ten siblings would have the defective gene. In our family, however, only three of the ten children have the defective gene. I know of other cases where all of the children have the defective gene. The only way to be sure is to take the DNA blood test for Kennedy's Disease.

Now, there is another misconception. Even if you have the mutated gene, that does not mean that you will have all the symptoms or when the onset of the disease will occur. Not everyone with the defective gene is going to respond the same. Onset could start as early as the teens (this is rare, however), or it could also start in the sixties. Normally, the onset will occur in the thirties or forties. One person in the family might have most of the symptoms, while another might have only some of the symptoms. The severity of the disorder is also not the same within a family. There is a belief, however, that the higher the number of CAG Repeats, the greater the severity.

So, when my father's sperm fertilized my mother's egg, I lost the coin flip (it came up tails = defective gene). I also have 53 CAG repeats (on the higher end = more severe).

No wonder I have never won the lottery! No, wait, perhaps it is because I never play the lottery.

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