Alternative splicing of the proteolipid protein 1 gene (PLP1) produces two forms, PLP1 and DM20, due to alternative use of 5' splice sites with the same acceptor site in intron 3. The PLP1 form predominates in central nervous system RNA. Mutations that reduce the ratio of PLP1 to DM20, whether mutant or normal protein is formed, result in the X-linked leukodystrophy Pelizaeus-Merzbacher disease...

Mutations in the gene for proteolipid protein (PLP) have been associated with CNS dysmyelination and abnormal oligodendrocyte death in spontaneous mouse mutants and in Pelizaeus-Merzbacher disease; however, the effect of mutations on PLP structure and function are little understood. We have identified a monoclonal antibody directed against a novel cell surface epitope of PLP, termed O10. By imm...

Pelizaeus-Merzbacher disease (PMD) is a dysmyelinating disease caused by mutations, deletions, or duplications of the proteolipid protein (PLP) gene. Mutant forms of PLP are retained in the endoplasmic reticulum (ER), and the resulting accumulation of mutant protein is thought to be a direct cause of oligodendrocyte cell death, which is the primary clinical feature of PMD. The molecular mechani...

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder with a prototype of a dysmyelinating leukodystrophy that is caused by a mutation in the proteolipid protein 1 (PLP1) gene on the long arm of the X chromosome in band Xq22. This mutation results in abnormal expression or production of PLP. We here present a Korean boy with spastic quadriplegia, horizontal nystagmus, saccadi...

Proton magnetic resonance spectroscopy (MRS) allows the noninvasive exploration of tissue metabolism in vivo, providing neurophysiological and neurochemical information. N-acetylaspartate (NAA) is generally considered to be a marker of neurons and axons, and many neurodegenerative disorders, including demyelinating disorders, exhibit a decrease in total NAA (tNAA). MRS in human hypomyelination ...

This chapter reviews the localizations and physiological roles of connexins in neurons and glia of the central and peripheral nervous systems. Cx32 forms gap junctions in noncompact myelin in Schwann cells, which are thought to form a reflexive communication pathway connecting the outer and inner myelin layers. Cx29 is also expressed in myelinating Schwann cells, but does not appear to form gap...

Evoked potentials were studied in 22 children with leukodystrophy [10 metachromatic leukodystrophy (MLD), 4 Pelizaeus-Merzbacher (PM), 3 Krabbes, 2 adrenoleukodystrophy (ALD), and one each of Alexander's, Canavan's and multiple sulphatase deficiency (MSD) diseases]. The ABRs were abnormal in all patients (except for the younger ALD), but varied with the type of leukodystrophy. The PM and Krabbe...

PMD (Pelizaeus-Merzbacher disease) is a rare neurodegenerative disorder that impairs motor and cognitive functions and is associated with a shortened lifespan. The cause of PMD is mutations of the PLP1 [proteolipid protein 1 gene (human)] gene. Transgenic mice with increased Plp1 [proteolipid protein 1 gene (non-human)] copy number model most aspects of PMD patients with duplications. Hypomyeli...

Leukoencephalopathies are diseases with high clinical heterogeneity. In clinical work, it's difficult for doctors to make a definite etiological diagnosis. Here, we designed a custom probe library which contains the known pathogenic genes reported to be associated with Leukoencephalopathies, and performed targeted gene capture and massively parallel sequencing (MPS) among 49 Chinese patients wh...

Oligodendrocytes are coupled by gap junctions (GJs) formed mainly by connexin47 (Cx47) and Cx32. Recessive GJC2/Cx47 mutations cause Pelizaeus-Merzbacher-like disease, a hypomyelinating leukodystrophy, while GJB1/Cx32 mutations cause neuropathy and chronic or acute-transient encephalopathy syndromes. Cx32/Cx47 double knockout (Cx32/Cx47dKO) mice develop severe CNS demyelination beginning at 1 m...