title: A (G-to-A) mutation in the initiation codon of the proteolipid protein gene causing a relatively mild form of Pelizaeus-Merzbacher disease in a Dutch family.
abstract: Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder that is characterized by dysmyelination of the central nervous system resulting from mutations in the proteolipid protein (PLP) gene. Mutations causing either overexpression or expression of a truncated form of PLP result in oligodendrocyte cell death because of accumulation of PLP in the endoplasmic reticulum. It has therefore been hypothesized that absence of the protein should result in a less severe phenotype. However, until now, only one patient has been described with a complete deletion of the PLP gene. We report a Dutch family with a relatively mild form of PMD, in which the disease cosegregates with a (G-to-A) mutation in the initiation codon of the PLP gene. This mutation should cause the total absence of PLP and is therefore in agreement with the hypothesis that absence of PLP leads to a mild form of PMD.
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
authors.forename: E A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: I J
authors.initials: IJ
authors.lastname: de Wijs
authors.forename: R F
authors.initials: RF
authors.lastname: de Coo
authors.forename: L M
authors.initials: LM
authors.lastname: Smit
authors.forename: F H
authors.initials: FH
authors.lastname: Menko
authors.forename: B A
authors.initials: BA
authors.lastname: van Oost
mesh_terms: D000328:Adult; D001483:Base Sequence; D018387:Codon, Initiator / Q000235:genetics*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D009426:Netherlands; D010375:Pedigree
chemical_list: D018387:Codon, Initiator; D018991:Myelin Proteolipid Protein