How HNPP relates to CMT

I found this interesting article with some good information explaining how CMT and HNPP relate.

Researchers Probe the Origins of Charcot-Marie-Tooth Disease
by Dan Stimson

(this is a portion of the article, click the title link for the full version)

CMT1A and HNPP: Flip Sides of the Same Coin
In the late 1980s, while the CMT gene hunt was gaining momentum, neurologist Phillip Chance was searching for the genetic cause of an apparently unrelated neuropathy — hereditary neuropathy with liability to pressure palsies (HNPP). To his surprise, Chance's investigation revealed that HNPP and most CMT1 cases result from the same mutation event. Once that mutation occurs, the emergence of either HNPP or CMT1 in a family is sort of like flipping a coin.HNPP is an inherited disorder that causes temporary attacks of paralysis typically localized to a single limb. Those attacks take weeks to months to recover from, and are brought on by palsy — the malfunction of a peripheral nerve that serves the affected limb. "[HNPP] is so different clinically from CMT," says Chance, "that few people suspected it had anything to do with CMT." But in 1992, Chance published an MDA-funded study showing that HNPP is genetically related to the most common form of CMT1 — CMT1A. Earlier that year, MDA-funded researchers had established that CMT1A is caused by a duplication of the PMP22 gene on chromosome 17. (It's important to remember that, except for the X and Y chromosomes, everyone normally has two copies of each chromosome, one from dad's sperm and one from mom's egg. So, having the duplication means that a person has three copies of the PMP22 gene.) The resulting overproduction of the PMP22 protein — a component of myelin — is somehow detrimental to Schwann cells.Though it's a rare event, the duplication usually arises while single copies of dad's chromosomes are being parceled into his sperm. As his two copies of chromosome 17 are preparing for separation into the sperm, a piece of genetic material containing PMP22 is accidentally removed from one copy of the chromosome and inserted into the other. So, one sperm receives an extra PMP22 gene, and one sperm loses its PMP22 gene. "The existence of the duplication predicted that there would be a reciprocal deletion, but it was generally assumed that the deletion would be lethal, of no consequence, or it could have resulted in a disorder which wasn't necessarily a peripheral neuropathy," says Chance, who's now at the University of Washington in Seattle.Chance's research showed that deletion of the PMP22 gene — the flip side of the mutation underlying CMT1A — is the cause of HNPP. "We had no reason to think that studying HNPP would give us any particular insights into CMT," says Chance. But it has helped make clear that peripheral nerve is sensitive to high or low levels of PMP22.

"The relationship with CMT has also done a lot to bring HNPP into the clinical arena," says Chance.