Encyclopedia
myelin protein zero
- genes
1. Introduction
The MPZ gene provides instructions for making a protein called myelin protein zero. It is the most abundant protein in myelin, a protective substance that covers nerves and promotes the efficient transmission of nerve impulses. Myelin protein zero is produced by specialized cells called Schwann cells, which wrap around and insulate peripheral nerves. Peripheral nerves connect 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 is an adhesion molecule, which means it acts like molecular glue. It plays a role in tightly packing the myelin around nerve cells (myelin compaction).
2. Health Conditions Related to Genetic Changes
2.1. Charcot-Marie-Tooth disease
Researchers have identified more than 120 MPZ gene mutations that cause a form of Charcot-Marie-Tooth disease known as type 1B. Charcot-Marie-Tooth syndrome is a disorder characterized by muscle weakness and sensory problems, especially in the hands and feet. Many of the MPZ gene mutations that cause Charcot-Marie-Tooth syndrome change single protein building blocks (amino acids) in myelin protein zero. Other 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 myelin compaction. As a result, peripheral nerves cannot trigger muscle movement or relay information from sensory cells back to the brain, leading to the weakness and sensory problems characteristic of Charcot-Marie-Tooth disease.
Some MPZ gene mutations cause a severe form of type 1B Charcot-Marie-Tooth disease. Symptoms begin during infancy or early childhood and include delayed development of motor skills such as walking. This form of Charcot-Marie-Tooth disease is sometimes called Dejerine-Sottas syndrome, congenital hypomyelination, or Roussy-Levy syndrome. Researchers believe that the MPZ gene mutations that cause the severe form of the disorder 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, which often do not become evident until adulthood, 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 gene mutations cause these abnormalities.
3. Other Names for This Gene
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CMT1B
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CMT2I
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CMT2J
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HMSN1B
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MPP
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myelin glycoprotein P-zero
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myelin peripheral protein
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myelin protein zero (Charcot-Marie-Tooth neuropathy 1B)
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MYP0_HUMAN
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P0 Glycoprotein
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P0 Protein
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/mpz
References
- Berger P, Niemann A, Suter U. Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease). Glia. 2006Sep;54(4):243-57. Review.
- Bird TD. Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview. 1998 Sep 28[updated 2020 May 14]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): Universityof Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1358/
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- Brennan KM, Bai Y, Shy ME. Demyelinating CMT--what's known, what's new andwhat's in store? Neurosci Lett. 2015 Jun 2;596:14-26. doi:10.1016/j.neulet.2015.01.059.
- Grandis M, Vigo T, Passalacqua M, Jain M, Scazzola S, La Padula V, Brucal M,Benvenuto F, Nobbio L, Cadoni A, Mancardi GL, Kamholz J, Shy ME, Schenone A.Different cellular and molecular mechanisms for early and late-onset myelinprotein zero mutations. Hum Mol Genet. 2008 Jul 1;17(13):1877-89. doi:10.1093/hmg/ddn083.
- Kochański A. Mutations in the Myelin Protein Zero result in a spectrum ofCharcot-Marie-Tooth phenotypes. Acta Myol. 2004 May;23(1):6-9. Review.
- Mandich P, Fossa P, Capponi S, Geroldi A, Acquaviva M, Gulli R, Ciotti P,Manganelli F, Grandis M, Bellone E. Clinical features and molecular modelling of novel MPZ mutations in demyelinating and axonal neuropathies. Eur J Hum Genet.2009 Sep;17(9):1129-34. doi: 10.1038/ejhg.2009.37.
- Niemann A, Berger P, Suter U. Pathomechanisms of mutant proteins inCharcot-Marie-Tooth disease. Neuromolecular Med. 2006;8(1-2):217-42. Review.
- Numakura C, Lin C, Ikegami T, Guldberg P, Hayasaka K. Molecular analysis inJapanese patients with Charcot-Marie-Tooth disease: DGGE analysis for PMP22, MPZ,and Cx32/GJB1 mutations. Hum Mutat. 2002 Nov;20(5):392-8.
- Shy ME. Peripheral neuropathies caused by mutations in the myelin proteinzero. J Neurol Sci. 2006 Mar 15;242(1-2):55-66.
- Warner LE, Hilz MJ, Appel SH, Killian JM, Kolodry EH, Karpati G, Carpenter S, Watters GV, Wheeler C, Witt D, Bodell A, Nelis E, Van Broeckhoven C, Lupski JR.Clinical phenotypes of different MPZ (P0) mutations may includeCharcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination.Neuron. 1996 Sep;17(3):451-60.
