Neuropathology and genetics of Pelizaeus-Merzbacher disease.
The recent history of Pelizaeus-Merzbacher Disease (PMD) demonstrates paradigmatically the impact of basic biological research on clinical neurology and brain pathology: this rare and peculiar hereditary disease has become one of the best known disorders of its kind, through a cooperative research effort in neuropathology, human genetics, neurochemistry and molecular biology. PMD, a genetic dysmyelination restricted to the CNS, has been identified as a disease that involves the X chromosome-linked gene for myelin proteolipid protein (PLP), a major structural myelin component. Today more than 30 different mutations in this gene have been defined and associated with PMD or the clinically distinct form X-linked spastic paraplegia type-2 (SPG-2). Improved scanning techniques, specifically the non-invasive magnetic resonance imaging (MRI), allow its early diagnosis in the heterogeneous group of CNS myelin deficiencies. These remarkable achievements have, at the same time, caused a problem for disease classification. Myelin disorders have been grouped in the past on the basis of clinical and neuropathological criteria, creating a system that has now to be reconciled with molecular-genetic data.
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D000818:Animals; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D008040:Genetic Linkage; D006801:Humans; D009154:Mutation; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D014960:X Chromosome