Unlike other leukodystrophies in which there is a period of normal cortical myelination an then comes a disruption resulting in the lost of myelin sheaths (demyelination), PMD has, from the beginning, an abnormal or low production of this very important protein (hypomyelination), due to a damage on the PLP1 gene coding for the Protelipidic Protein type 1 that interferes with the oligodendrocyte synthesis of fully functional myelin sheaths and probably also affects the peripheral function of myelinated axons (3,8).
PMD corresponds to a larger group of neurological phenotypes known as PLP1 related disorders, all being allelic diseases: Connatal PMD, Classic PMD, Nule Syndrome (NS), Complicated Hereditary Spastic Paraplegia type 2 (SPG2) and Uncomplicated Spastic Paraplegia type 2, ranging in a wide variety of clinical manifestations which variability is not yet completely understood (5,9).
Thurston et al., "Genomic rearrangements resulting in PLP1
deletion occur by nonhomologous end joining and cause different dysmyelinatingphenotypes in males and females," American Journal of Human Genetics, vol.
There are point mutations in PLP1 gene at the region of X q21-223 leading to micro- deletion or duplication of the aminoacids involved in the formation of oligodendrocytes required for myelination of the brain and spinal cord.
Variable Expression of a Novel PLP1 Mutation in Members of a Family With Pelizaeus-Merzbacher Disease.
However, PMD patients who have PLP1 mutations that cause greatly reduced amounts of PLP, but not DM20, or mutant mice expressing DM20, but not PLP, show a slow disintegration of the compact layers of the myelin sheath with aging, which also suggests a role for the intracellular loop of PLP in stabilizing compact myelin [8-10].
Jain et al., "Schwanncell expression of PLP1 but not DM20 is necessary to prevent neuropathy," Annals of Neurology, vol.
AR and PGK1 are located near the OGT, and PLP1
, TBG, and CAPN6 are located around 100 Mb on SSC X.
We did not find any signal for the gene products of the genes family member 1, proteolipid protein 1, neuronatin, or olfactomedin 1 (ZIC1, PLP1
, NNAT, or OLFM1) with the antibodies described in Table 3.
Pelizaeus-Merzbacher disease (PMD) (9) and the allelic disorder spastic paraplegia type 2 (SPG2) are rare X-linked recessive dysmyelination disorders caused by sequence variations in the proteolipid protein 1 (PLP1
)  gene (1-3).
Spastic paraplegia type 2 associated with axonal neuropathy and apparent PLP1
We selected the results of screening the TCM database@Taiwan based on PLP1
and PLP2 being better than anthocyanin, and then ranked the docking score (Table 2).