Study Shows How Extra PMP22 Gene in Patients with CMT1A May Cause Cellular Toxicity

According to Charcot-Marie-Tooth News, patients with Charcot-Marie-Tooth disease type 1A (CMT1A) have an extra PMP22 gene. However, new research shows that this excess gene causes a toxic accumulation of protein within cells. Because extra PMP22 protein does not fold properly, it disrupts cells. Now, researchers believe this may cause CMT1A progression. Read the full findings in Journal of Biological Chemistry.

PMP22 Gene

Generally, researchers believe the PMP22 gene maintains myelin, a protective covering over nerve cells. Normally, PMP22 encodes a protein of the same name which is transported to the surface of cells. Most people have two of these genes. However, in patients with CMT1A, a 3rd copy prompts disease development.

Researchers hypothesized that this extra protein interrupted the cell’s ability to fold proteins properly. If a protein is improperly folded, it cannot be transported to its correct cellular spot. As a result, toxic protein clumps built up, causing health difficulties.

First, researchers analyzed how quickly and at what rate cells transported the PMP22 protein from the endoplasmic reticulum to the plasma membrane. Next, they analyzed how this changed as the protein accumulated. Even though protein was still being transported to the plasma membrane, the cell was unable to unload extra protein within the ER. Then, researchers used mice models of CMT and CMT1A. They found that, in addition to cellular overload, different PMP22 gene mutations contributed to disease progression and patient outcomes.

Charcot-Marie-Tooth Disease

Caused by genetic mutations, Charcot-Marie-Tooth disease (CMT) is a rare inherited neurological disorder. There are multiple subsets of CMT, all of which depend on specific gene mutations. However, in all cases, patients experience peripheral nerve degeneration. As a result, the muscles and nerves fail to communicate. Generally, symptoms appear in adolescence or early childhood. In rare cases, CMT onset occurs in adulthood. Symptoms include:

  • Loss of fine motor skills
  • Difficulty walking or climbing
  • Foot and leg muscle weakness
  • Foot drop
  • Muscle loss in the lower extremities
  • Muscle weakness and atrophy in the hands

Learn more about CMT.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

Share this post

Share on facebook
Share on google
Share on twitter
Share on linkedin
Share on pinterest
Share on print
Share on email
Close Menu