Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder characterized by dysmyelination in the central nervous system. PMD results from deletion, mutation, or duplication of the proteolipid protein gene (PLP1) located at Xq22, leading to the failure of axon myelination by oligodendrocytes in the central nervous system. PMD may be suspected when there are clinical manifestation...

The two proteins, proteolipid protein and DM20, which are encoded by alternative transcripts from the proteolipid protein ( PLP ) gene, are major components of central nervous system myelin. In man, mutations of these proteins cause Pelizaeus-Merzbacher disease (PMD), an X-linked dysmyelinating neuropathy. The mutations found are very varied, ranging from deletions, loss-of-function and missens...

The pediatric leukodystrophies comprise a category of disease manifested by neonatal or childhood deficiencies in myelin production or maintenance; these may be due to hereditary defects in one or more genes critical to the initiation of myelination, as in Pelizaeus-Merzbacher Disease, or to enzymatic deficiencies with aberrant substrate accumulation-related dysfunction, as in the lysosomal sto...

Pelizaeus-Merzbacher disease (PMD) is a hypomyelinating leukodystrophy caused by mutations of the proteolipid protein 1 gene (PLP1), which is located on the X chromosome and encodes the most abundant protein of myelin in the central nervous sytem. Approximately 60% of PMD cases result from genomic duplications of a region of the X chromosome that includes the entire PLP1 gene. The duplications ...

PMD (Pelizaeus-Merzbacher disease), a CNS (central nervous system) disease characterized by shortened lifespan and severe neural dysfunction, is caused by mutations of the PLP1 (X-linked myelin proteolipid protein) gene. The majority of human PLP1 mutations are caused by duplications; almost all others are caused by missense mutations. The cellular events leading to the phenotype are unknown. T...

Chromosome structural changes with nonrecurrent endpoints associated with genomic disorders offer windows into the mechanism of origin of copy number variation (CNV). A recent report of nonrecurrent duplications associated with Pelizaeus-Merzbacher disease identified three distinctive characteristics. First, the majority of events can be seen to be complex, showing discontinuous duplications mi...

PURPOSE To determine whether pontomedullary corticospinal tract involvement is a common and specific finding of adrenoleukodystrophy on MR images. METHODS MR images of 10 patients with biochemically proved adrenoleukodystrophy who were examined during the last 6 years were reviewed retrospectively to determine the frequency of corticospinal tract involvement in the medulla, pons, mesencephalo...

PURPOSE To investigate the MR findings of childhood metachromatic leukodystrophy (MLD). METHODS Nine MR imaging studies in seven children (five girls and two boys, 10 to 32 months old) with MLD were evaluated retrospectively for the extent and progression of white matter abnormalities and the presence of contrast enhancement. RESULTS All seven cases showed symmetric, confluent high signal i...

In the present overview, practical application of the visual evoked potential (VEP) in paediatric neuro-ophthalmology is described across a wide range of ophthalmogenetic disorders, including albinism, Pelizaeus-Merzbacher disease and spastic paraplegia. The VEP approach is based on a four parameter subdivision of the electrophysiological response which includes, (1) amplitude (microV), (2) lat...

Duplications and overexpression of the proteolipid protein (PLP) gene are known to cause the dysmyelinating disorder Pelizaeus-Merzbacher disease (PMD). To understand the cellular response to overexpressed PLP in PMD, we have overexpressed PLP in BHK cells and primary cultures of oligodendrocytes with the Semliki Forest virus expression system. Overexpressed PLP was routed to late endosomes/lys...