title: A novel proteolipid protein 1 gene mutation causing classical type Pelizaeus-Merzbacher disease.
abstract: Pelizaeus-Merzbacher disease (PMD) is a rare dysmyelinating disorder caused by mutations in the proteolipid protein 1 (PLP1) gene. PMD is generally classified according to its clinical or pathological features into classical or connatal forms. We describe here a 19-year-old male with classical form PMD who presented with stridor and nystagmus in early infancy and whose psychomotor development has been severely delayed. Brain magnetic resonance imaging revealed white matter abnormalities typical of PMD. Direct sequencing of the PLP1 gene identified two nucleotide substitutions. One was a C-to-T transition at -31 in the 5'-flanking region of exon 1; the other was a novel point mutation, T-to-C transition in exon 4, which led to substitution of cysteine for arginine at residue 184. Because Cys184 forms a disulphide bridge with Cys228, the Cys184Arg mutation probably removes the bridge and changes the tertiary structure of PLP protein. A defective disulfide bond in PLP protein could be important in the pathogenesis of PMD.
authors.affiliation: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. fukumura@sapmed.ac.jp
authors.forename: Shinobu
authors.initials: S
authors.lastname: Fukumura
authors.forename: Noriaki
authors.initials: N
authors.lastname: Adachi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nagao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsumi
mesh_terms: D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000737:chemistry / Q000235:genetics*; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics*; D011487:Protein Conformation; D055815:Young Adult
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human