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Genetics Home Reference: your guide to understanding genetic conditions
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PMP22

Reviewed January 2010

What is the official name of the PMP22 gene?

The official name of this gene is “peripheral myelin protein 22.”

PMP22 is the gene's official symbol. The PMP22 gene is also known by other names, listed below.

What is the normal function of the PMP22 gene?

The PMP22 gene provides instructions for making a protein called peripheral myelin protein 22. This protein is found in the peripheral nervous system, which connects the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.

Peripheral myelin protein 22 is a component of myelin, a protective substance that covers nerves and promotes the efficient transmission of nerve impulses. The protein is produced primarily by specialized cells called Schwann cells that wrap around and insulate nerves. Within Schwann cells, peripheral myelin protein 22 plays a crucial role in the development and maintenance of myelin. The PMP22 gene may also play a role in Schwann cell growth and differentiation (the process by which cells mature to carry out specific functions).

Before it becomes part of myelin, newly produced peripheral myelin protein 22 is processed and packaged in specialized cell structures called the endoplasmic reticulum and the Golgi apparatus. Completion of these processing and packaging steps is critical for proper myelin function.

How are changes in the PMP22 gene related to health conditions?

Charcot-Marie-Tooth disease - caused by mutations in the PMP22 gene

Mutations in the PMP22 gene cause forms of Charcot-Marie-Tooth disease known as types 1A and 1E.

An extra copy of the PMP22 gene in each cell is the most common genetic change that causes type 1A Charcot-Marie-Tooth disease. The extra gene leads to an overproduction of peripheral myelin protein 22, which prevents the protein from being processed correctly. A reduced amount of functional peripheral myelin protein 22 impairs the formation of myelin. The unprocessed peripheral myelin protein 22 may also disrupt other Schwann cell activities, which leads to instability and loss of myelin (demyelination). Demyelination reduces the ability of the peripheral nerves to activate muscles used for movement or relay information from sensory cells back to the brain, causing the signs and symptoms of type 1A Charcot-Marie-Tooth disease.

Type 1A Charcot-Marie-Tooth disease is also caused by mutations that add, delete, or change the building blocks (amino acids) used to make peripheral myelin protein 22. The altered protein is probably processed at a slower rate, and some of the protein is processed abnormally. These disruptions of peripheral myelin protein 22 processing impair the normal functions of the Schwann cell, leading to demyelination and producing the signs and symptoms of type 1A Charcot-Marie-Tooth disease.

Hearing loss is experienced by some people with a form of type 1 Charcot-Marie-Tooth disease called type 1E. Type 1E is associated with particular amino acid substitutions and deletions in the PMP22 gene. The most frequently reported mutation causing hearing loss replaces the amino acid alanine with the amino acid proline at protein position 67 (also written as Ala67Pro).

hereditary neuropathy with liability to pressure palsies - caused by mutations in the PMP22 gene

Loss of one copy of the PMP22 gene from each cell is the most common genetic cause of hereditary neuropathy with liability to pressure palsies. Deletion of one copy of the PMP22 gene (also called reduced gene dosage) probably decreases the amount of peripheral myelin protein 22 available for myelin production. This disorder is also caused by PMP22 gene mutations that produce an abnormally small protein, which is rapidly broken down. Other mutations change one of the amino acids used to make peripheral myelin protein 22, producing an unstable protein. A reduction in the amount of stable protein leads to the loss of myelin. Demyelination results in increased sensitivity to pressure on the nerves, causing the signs and symptoms of hereditary neuropathy with liability to pressure palsies.

Where is the PMP22 gene located?

Cytogenetic Location: 17p12

Molecular Location on chromosome 17: base pairs 15,229,776 to 15,265,356

The PMP22 gene is located on the short (p) arm of chromosome 17 at position 12.

The PMP22 gene is located on the short (p) arm of chromosome 17 at position 12.

More precisely, the PMP22 gene is located from base pair 15,229,776 to base pair 15,265,356 on chromosome 17.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PMP22?

You and your healthcare professional may find the following resources about PMP22 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the PMP22 gene or gene products?

  • GAS-3
  • growth arrest-specific 3
  • HNPP
  • MGC20769
  • PMP22_HUMAN
  • Sp110

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PMP22?

acids ; alanine ; amino acid ; cell ; deletion ; demyelination ; differentiation ; endoplasmic reticulum ; gene ; gene dosage ; Golgi apparatus ; hereditary ; mutation ; nervous system ; neuropathy ; peripheral ; peripheral nerves ; peripheral nervous system ; proline ; protein ; Schwann cells ; sensitivity ; sensory cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Al-Thihli K, Rudkin T, Carson N, Poulin C, Melançon S, Der Kaloustian VM. Compound heterozygous deletions of PMP22 causing severe Charcot-Marie-Tooth disease of the Dejerine-Sottas disease phenotype. Am J Med Genet A. 2008 Sep 15;146A(18):2412-6. doi: 10.1002/ajmg.a.32456. (http://www.ncbi.nlm.nih.gov/pubmed/18698610?dopt=Abstract)
  • Berger P, Young P, Suter U. Molecular cell biology of Charcot-Marie-Tooth disease. Neurogenetics. 2002 Mar;4(1):1-15. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12030326?dopt=Abstract)
  • Jetten AM, Suter U. The peripheral myelin protein 22 and epithelial membrane protein family. Prog Nucleic Acid Res Mol Biol. 2000;64:97-129. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10697408?dopt=Abstract)
  • Katona I, Wu X, Feely SM, Sottile S, Siskind CE, Miller LJ, Shy ME, Li J. PMP22 expression in dermal nerve myelin from patients with CMT1A. Brain. 2009 Jul;132(Pt 7):1734-40. doi: 10.1093/brain/awp113. Epub 2009 May 15. (http://www.ncbi.nlm.nih.gov/pubmed/19447823?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5376)
  • Niedrist D, Joncourt F, Mátyás G, Müller A. Severe phenotype with cis-acting heterozygous PMP22 mutations. Clin Genet. 2009 Mar;75(3):286-9. doi: 10.1111/j.1399-0004.2008.01120.x. Epub 2008 Nov 29. (http://www.ncbi.nlm.nih.gov/pubmed/19067730?dopt=Abstract)
  • Niemann A, Berger P, Suter U. Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease. Neuromolecular Med. 2006;8(1-2):217-42. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16775378?dopt=Abstract)
  • Young P, Suter U. The causes of Charcot-Marie-Tooth disease. Cell Mol Life Sci. 2003 Dec;60(12):2547-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14685682?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2010
Published: August 25, 2014