Jim, I'm a little confused, are you saying your grandfather was two or your mom was 2 years old? It does sound like this exposure could have something to do with your KD after reading Dan's info.

Dave, I'm so sorry your family has been hit so bad. Do you now think your grandfather actually had KD? As I said, my husband uncle was told he has ALS but I doubt it all these years later. He never would go through all the testing that Bob went through. He lives on the east coast so we never see him. Did you nephew have the genetic blood test? What age was he when he showed symptoms? Look into your family past to see if you can find any exposures to anything.

I would seriously doubt that exposure to mustard gas (or any mutagen) would cause KD in an individual. First of all, the mutation in KD is a very unique one that cannot be caused by a chemical change to the gene. This is not to say that mustard gas cannot cause mutations, but that the mechanism by which is does so would not likely cause a change in CAG repeat number.

Second, even if mustard gas could cause the increase in the CAG repeats, to get KD, you need to have the mutated allele in your motor neurons. Motor neurons are cells that are produced very early in life and our bodies cannot produce new ones, thus to give them KD, you have to alter each one individually. Thus, the mutation would have to occur independently thousands of times in different motor neurons in the spinal cord and brain. This is so unlikely as to be essentially not possible.

Then, even if this were to occur, acquired mutations in cells such as neurons would not be passed on to children as neurons are not the source of sperm (or eggs). Thus, there would have to be another (rare) mutation (of the same kind) in your germ cells, the cells that produce sperm. This just makes this all the more unlikely as a source of the KD mutation.

There is another, much more common explanation for this mutation. Everyone, whether they have KD or not, has in the Androgen Receptor gene (the gene affected in KD), has a CAG repeat. The length of this repeat can vary in different individuals. When this repeat exceeds 40, KD results. It has been noticed that the number of repeats can vary within an individual as they age. Essentially, this is due to mistakes in the processing of the DNA. While the number of repeats can increase and decrease, the overall trend is to increase. Thus it would be possible for a person with 34 repeats at birth, to have cells with over 40 repeats when they are older (only, I should add, in some cells - it is very unlikely that it can occur in number enough to cause KD in this person). If, however, the expansion of the repeat number occurs in germ cell, then the >40 repeat would be passed on to their children.

I am writing this quickly, so I hope that it makes sense. The bottom line is that it is not necessary to invoke a mutagen to explain the origin of KD.

BTW, KD is a dominant allele, not recessive. It was originally thought to be recessive but they were wrong.

I think one problem with trying to find a "founder" for KD within a family is that up until the early 20th century, the average life expectancy was too short to be able to see the more severe muscle weakness, so it would be tough to be determine of some of the individuals has KD or not.

There is a founding father effect among the Anishinabe of North West Ontario, which as a Metis, is my link to KD. I understand the intital diagnosis of the disease resulted from a Metis man from Minnesota, probably a long lost cousin.