Pelizaeus-Merzbacher disease and spastic paraplegia type 2: two faces of myelin loss from mutations in the same gene.
Pelizaeus-Merzbacher disease and X-linked spastic paraplegia type 2 are two sides of the same coin. Both arise from mutations in the gene encoding myelin proteolipid protein. The disease spectrum for Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is extraordinarily broad, ranging from a spastic gait in the pure form of spastic paraplegia type 2 to a severely disabling form of Pelizaeus-Merzbacher disease featuring hypotonia, respiratory distress, stridor, nystagmus, and profound myelin loss. The diverse disease spectrum is mirrored by the underlying pathogenesis, in which a blockade at any stage of myelin proteolipid protein synthesis and assembly into myelin spawns a unique phenotype. The continuing definition of pathogenetic mechanisms operative in Pelizaeus-Merzbacher disease and spastic paraplegia type 2, together with advances in neural cell transplant therapy, augurs well for future treatment of the severe forms of Pelizaeus-Merzbacher disease.
Section of Developmental Genetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36, Room 5D06, 36 Convent Dr, MSC 4160, Bethesda, MD 20892-4160, USA. hudsonl@ninds.nih.gov
Lynn D
LD
Hudson
D000483:Alleles; D000818:Animals; D003711:Demyelinating Diseases; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009186:Myelin Sheath / Q000473:pathology*; D010264:Paraplegia / Q000235:genetics*; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics*
D018991:Myelin Proteolipid Protein