title: Nonsense mutation in exon 3 of the proteolipid protein gene (PLP) in a family with an unusual form of Pelizaeus-Merzbacher disease.
abstract: We report a G-->A transition at nucleotide 431 of the proteolipid protein gene (PLP) results in a nonsense codon in a family with an unusual form of Pelizaeus-Merzbacher disease (PMD). The mutation, which creates a second AluI restriction site, results in a nonsense mutation in PLP. The clinical picture resembles somewhat that of X-linked spastic paraplegia (SPG). It differs from this and both the classical and connatal forms of PMD in that it is relatively mild in form, onset is delayed beyond age 2 years, nystagmus is absent, tremors are prominent, mental retardation is not severe, some patients show dementia or personality disorders, the disease is progressive rather than static in some, and several females show signs of disease. The nonsense mutation, which is in exon 3B, should block the synthesis of normal PLP but spare DM20, the isoform whose persistence has been associated with mild forms of PLP-associated disease in both humans and mice.
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5251, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Hodes
authors.forename: C A
authors.initials: CA
authors.lastname: Blank
authors.forename: V M
authors.initials: VM
authors.lastname: Pratt
authors.forename: J
authors.initials: J
authors.lastname: Morales
authors.forename: J
authors.initials: J
authors.lastname: Napier
authors.forename: S R
authors.initials: SR
authors.lastname: Dlouhy
mesh_terms: D000293:Adolescent; D000328:Adult; D017931:DNA Primers; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D018991:Myelin Proteolipid Protein