title: Mutation of the proteolipid protein gene PLP in a human X chromosome-linked myelin disorder.
abstract: Myelin is a highly specialized membrane unique to the nervous system that ensheaths axons to permit the rapid saltatory conduction of impulses. The elaboration of a compact myelin sheath is disrupted in a diverse spectrum of human disorders, many of which are of unknown etiology. The X chromosome-linked human disorder Pelizaeus-Merzbacher disease is a clinically and pathologically heterogeneous group of disorders that demonstrate a striking failure of oligodendrocyte differentiation. This disease appears pathologically and genetically to be similar to the disorder seen in the dysmyelinating mouse mutant jimpy, which has a point mutation in the gene encoding an abundant myelin protein, proteolipid protein (PLP). We report that the molecular defect in one Pelizaeus-Merzbacher family is likewise a point mutation in the PLP gene. A single T----C transition results in the substitution of a charged amino acid residue, arginine, for tryptophan in one of the four extremely hydrophobic domains of the PLP protein. The identification of a mutation in this Pelizaeus-Merzbacher family should facilitate the molecular classification and diagnosis of these X chromosome-linked human dysmyelinating disorders.
authors: Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
authors: L D
authors: LD
authors: Hudson
authors: C
authors: C
authors: Puckett
authors: J
authors: J
authors: Berndt
authors: J
authors: J
authors: Chan
authors: S
authors: S
authors: Gencic
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003711:Demyelinating Diseases / Q000235:genetics; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D005091:Exons; D005796:Genes; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics*; D018991:Myelin Proteolipid Protein; D012016:Reference Values; D015183:Restriction Mapping; D014960:X Chromosome
chemical_list: D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein