MPZ

The MPZ gene provides instructions for making a protein called myelin protein zero. It is the most abundant protein in the myelin sheath, the covering that protects nerves and promotes the efficient transmission of nerve impulses. Specialized cells called Schwann cells are the only cells that make myelin protein zero. Schwann cells are part of the peripheral nervous system that connects the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Myelin protein zero is required for the proper formation and maintenance of myelin. This protein acts like a molecular glue (adhesion molecule) and plays a role in tightly packing the myelin (myelin compaction).

From inside Schwann cells, myelin protein zero is inserted through the cell membrane, the structure that encloses a cell. One end of the protein remains inside the cell and is called the intracellular domain. The other end of the protein pokes through the membrane to the outside of the cell; this part of the protein is called the extracellular domain. The extracellular domain interacts with other substances that make up the myelin sheath. The section of myelin protein zero that spans the cell membrane is called the transmembrane domain.

Charcot-Marie-Tooth disease - caused by mutations in the MPZ gene

Researchers have identified more than 100 MPZ mutations that cause a form of Charcot-Marie-Tooth known as type 1B. Many of these mutations alter the extracellular domain by replacing one of the building blocks (amino acids) in myelin protein zero with an incorrect amino acid. Other MPZ mutations lead to a protein that is missing one or more amino acids. The altered myelin protein zero probably cannot interact properly with other myelin components, which may disrupt the formation and maintenance of the myelin sheath. As a result, peripheral nerve cells cannot activate muscles used for movement or relay information from sensory cells back to the brain, causing the signs and symptoms of type 1B Charcot-Marie-Tooth disease.

Some MPZ mutations cause severe symptoms of type 1B Charcot-Marie-Tooth disease that begin during infancy or early childhood. (The early-onset forms are sometimes called Dejerine-Sottas syndrome, congenital hypomyelination, or Roussy-Levy syndrome.) Researchers believe that these mutations probably disrupt the formation of myelin during early development.

Several mutations in the MPZ gene cause other forms of Charcot-Marie-Tooth disease known as type 2I, type 2J, and dominant intermediate D. These forms of Charcot-Marie-Tooth disease affect the specialized outgrowths from nerve cells (axons) that transmit impulses to muscles and other nerve cells. People with type 2J Charcot-Marie-Tooth disease may also have hearing loss and abnormalities in the opening of the eye through which light passes (the pupil). It is unclear how MPZ mutations cause these abnormalities.