title: A novel insertional mutation at exon VII of the myelin proteolipid protein gene in Pelizaeus-Merzbacher disease.
abstract: Pelizaeus-Merzbacher disease (PMD) is an X-linked neurological disorder characterized by dysmyelination in the central nervous system (CNS). Recently mutations of the myelin proteolipid protein (PLP) gene which encodes both PLP and its isoform, DM-20 generated by alternative splicing, have been demonstrated in PMD patients. We analyzed the seven exons of the PLP gene of a Japanese boy affected with PMD by direct sequencing and identified an insertion event in exon VII of the PLP gene. This mutation was also present in his carrier mother, but was absent in ninety-five X chromosomes of normal Japanese. The frame-shift mutation leads to the production of truncated PLP with altered carboxyl terminal amino acid sequences, resulting in considerable change of the structure of PLP and DM-20 necessary for functional purposes. This is the first report of a mutation in exon VII of the PLP gene associated with PMD.
authors.affiliation: Institute of Genetic Information, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kurosawa
authors.forename: A
authors.initials: A
authors.lastname: Iwaki
authors.forename: S
authors.initials: S
authors.lastname: Miyake
authors.forename: K
authors.initials: K
authors.lastname: Imaizumi
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroki
authors.forename: Y
authors.initials: Y
authors.lastname: Fukumaki
mesh_terms: D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D017931:DNA Primers; D004251:DNA Transposable Elements; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics*; D018991:Myelin Proteolipid Protein; D016133:Polymerase Chain Reaction; D012016:Reference Values; D014960:X Chromosome
chemical_list: D017931:DNA Primers; D004251:DNA Transposable Elements; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein