Dejerine–Sottas disease , also known as, Dejerine–Sottas syndrome , hereditary motor and sensory polyneuropathy type III, and Charcot–Marie–Tooth disease type 3 , is a hereditary neurological disorder characterized by damage to the peripheral nerves , demyelination , and resulting progressive muscle wasting and somatosensory loss. The condition is caused by mutations in various genes and currently has no known cure.
16-445: P0 or p0 may refer to: P0 protein lppp Standard atmospheric pressure of 101325 Pa Neutronium , hypothetically occupying Period 0 in the periodic table Proflight Zambia IATA airline coo See also [ edit ] 0P (disambiguation) PO (disambiguation) [REDACTED] Topics referred to by the same term This disambiguation page lists articles associated with
32-399: A myelinating cell wraps its membrane around an axon multiple times, generating multiple layers of myelin, myelin protein zero helps keep these sheets compact by serving as a "glue" that keeps the layers of myelin together. It does so by holding its characteristic coil structure together by the electrostatic interactions of its positively charged intracellular domain with acidic lipids in
48-517: A smaller positively charged intracellular region (151–219). Its cytoplasmic domain is highly positively charged but presumably does not fold into a globular structure. The extracellular domain is structurally similar to the immunoglobulin domain and therefore the protein is considered as belonging to immunoglobulin superfamily . Besides existing as a monomer, myelin protein zero is also known to form dimers and tetramers with other myelin protein zero molecules in vertebrates. The myelin sheath
64-416: Is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction. Myelin protein zero, absent in the central nervous system, is a major component of the myelin sheath in peripheral nerves . Mutations that disrupt the function of myelin protein zero can lead to less expression of myelin and degeneration of myelin sheath in
80-646: Is a single membrane glycoprotein which in humans is encoded by the MPZ gene. P0 is a major structural component of the myelin sheath in the peripheral nervous system (PNS) . Myelin protein zero is expressed by Schwann cells and accounts for over 50% of all proteins in the peripheral nervous system, making it the most common protein expressed in the PNS. Mutations in myelin protein zero can cause myelin deficiency and are associated with neuropathies like Charcot–Marie–Tooth disease and Dejerine–Sottas disease . In humans,
96-497: Is caused by a genetic defect either in the proteins found in axons or the proteins found in myelin . Specifically, it has been associated with mutations in MPZ , PMP22 , PRX , and EGR2 genes . The disorder is inherited in an autosomal dominant or autosomal recessive manner. On medical imaging, the peripheral and cranial nerves are enlarged by redundant connective tissue . On histology , this enlargement gives
112-666: Is rare. Dejerine–Sottas disease is characterized by moderate to severe lower and upper extremity weakness and loss of sensation, mainly in the lower legs, forearms, feet, and hands. Loss of muscle mass and reduced muscle tone usually occur as the disease progresses. Other symptoms may include pain in the extremities, curvature of the spine, clawed hands, foot deformities, ataxia , peripheral areflexia , and slow acquisition of motor skills in childhood. Symptoms that are less common can include limitation of eye movements, other eye problems such as nystagmus or anisocoria , or moderate to severe hearing loss . Dejerine–Sottas neuropathy
128-414: Is slow until the teenage years at which point it may accelerate, resulting in severe disability. Symptoms are more severe and rapidly progressive than in the other more common Charcot–Marie–Tooth diseases . Some patients may never walk and will be reliant on wheelchair use by the end of their first decade, while others may need only a cane, crutches, or similar support through most of their lives, but this
144-474: The cytoplasmic face of the opposite bilayer. and by interaction between hydrophobic globular 'heads' of adjacent extracellular domains . Myelin protein zero's function is similar to the function of other proteins with immunoglobin domains like polyimmunoglobin and T4 protein. These proteins function as binding and adhesion molecules and participate in homotypic interactions, or interactions that involve two similar proteins. Myelin protein zero holds together
160-463: The cytoplasmic domain or changing the tertiary structure of myelin protein zero can also result in neuropathy because the cytoplasmic domain has been demonstrated to be necessary for homotypic interactions. Dejerine%E2%80%93Sottas disease The disorder is named for Joseph Jules Dejerine and Jules Sottas , French neurologists who first described it. Onset occurs in infancy or early childhood, usually before three years of age. Progression
176-431: The development of myelin early on in life or myelin degeneration on the axon later on in life. Some mutations can cause neuropathy in infancy like Derjerine-Sottas disease while other mutations can cause neuropathy within the first two decades of life like Charcot-Marie-Tooth disease . Adding a charged amino acid or changing a cysteine residue in the extracellular membrane can lead to neuropathy onset early on. Truncating
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#1732797203074192-536: The gene that encodes myelin protein zero is located on chromosome 1 near the Duffy locus or the Duffy antigen/chemokine receptor. The gene is about 7,000 bases long and is divided into 6 exons. In total, myelin protein zero is 219 amino acids long and has many basic amino acid residues. Myelin protein zero consists of an extracellular N-terminal domain (amino acids 1–124), a single transmembrane region (125–150), and
208-524: The myelin sheath by participating in homotypic interactions with other myelin protein zero proteins. Myelin protein zero's extracellular domain binds to the myelin sphingolipid membrane and holds together myelin layers using homotypic interactions with other myelin protein zero extracellular domains, and with extracellular tryptophan residues interacting with the membrane. Myelin protein zero has also been demonstrated to interact with other proteins like peripheral myelin protein 22 . However, at this point
224-471: The peripheral nervous system. Currently, myelin protein zero expression is postulated to be produced by signals from the axon. However, more details about the regulation of myelin protein zero are unknown. It is postulated that myelin protein zero is a structural element in the formation and stabilization of peripheral nerve myelin. Myelin protein zero is also hypothesized to serve as a cell adhesion molecule, holding multiple layers of myelin together. When
240-406: The purpose of these interactions has not yet been determined. Mutations in myelin protein zero are known to cause myelin degeneration and neuropathy . Mutations that reduce myelin protein zero's adhesion function or its ability to participate in homeotypic interactions with other myelin protein zero proteins are thought to cause neuropathy. Mutations to myelin protein zero can lead to issues with
256-795: The same title formed as a letter–number combination. If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=P0&oldid=1221011048 " Category : Letter–number combination disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages P0 protein 3OAI 4359 17528 ENSG00000158887 ENSMUSG00000056569 P25189 P27573 NM_000530 NM_001315491 NM_008623 NM_001315499 NM_001315500 NP_000521 NP_001302420 NP_001302428 NP_001302429 NP_032649 Myelin protein zero ( P0 , MPZ )
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