Myelination Charcot-marie-tooth disease

Wrabetz, L., Feltri, M. L. and Suter, U. Models of Charcot-Marie-Tooth disease. In R. A. Lazzarini (ed.), Myelin biology and disorders. San Diego, CA Elsevier Academic Press, 2004, 1143-1168. 

Hattori, N., Yamamoto, M., Yoshihara, T. et al. Study Group for Hereditary Neuropathy in Japan. Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32) a clinicopathological study of 205 Japanese patients. Brain 126 134-151,2003. 

Charcot-Marie-Tooth disease and other inherited neuropathies AD, AR or X-linked PMP-22, P0, connexin-32 and other genes Variable degrees of myelin deficiency specific for the PNS see text 1,28-30... 

As noted in the preceding section, Cx32 is a ubiquitous protein that is also found in CNS myelin. Its presence in Schwann cells was discovered when Cx32 mutations were associated with Charcot-Marie-Tooth disease of the CMTX type. CMTX is an X-linked demyelinating neuropathy. The molecule is located in the paranodes. There are subtle anomalies of the myelin sheath and the Ranvier node (Hahn et al.,... 

Trask BJ, Pentao L, et al. The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type lA. Nature Genet 1992 1 159-65. 

The importance of P0 in PNS myelin has been clearly demonstrated. In P0 gene knockout experiments in mice [40], severe hypomyelination and a virtual absence of compact myelin in the PNS is observed. In humans, there are two disease states associated with mutations in the P0 gene Charcot-Marie-Tooth type I disease (see Ch. 38) and Dejerine-Sottas disease, both dysmyelinating diseases that exhibit a spectrum of severity depending on the particular mutation. 

Other demyelinating diseases also exist, and their cause is much more straightforward. These are relatively rare disorders. In all of these diseases, there is no fully effective treatment for the patient. Inherited mutations in Po (the major PNS myelin protein) leads to a version of Charcot-Marie-Tooth polyneuropathy syndrome. The inheritance pattern for this disease is autosomal dominant, indicating that the expression of one mutated allele will lead to expression of the disease. Mutations in PEP (the major myelin protein in the CNS) lead to Pelizaeus-Merzbacher disease and X-linked spastic paraplegia type 2 disease. These diseases display a wide range of phenotypes, from a lack of motor development and early death (most severe) to mild gait disturbances. The phenotype displayed depends on the precise location of the mutation within the protein. An altered function of either Po or PLP leads to demyelination and its subsequent clinical manifestations. 

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