title: Pelizaeus-Merzbacher disease as a chromosomal disorder.
abstract: Pelizaeus-Merzbacher disease (PMD) is a congenital hypomyelination disorder caused by alterations affecting the proteolipid protein 1 gene (PLP1) located on Xq22.2. Generally, patients with PLP1 missense mutations show the most severe form of PMD (connatal form); however, two-thirds of patients with PMD carry PLP1 duplications and present typical manifestations of the disorder, recognized as the classical form. Other rare PLP1 abnormalities have been also identified, including X-chromosome translocations, triplications, and a partial duplication, all involving PLP1. The genomic structure of the distal end of the PLP1 locus, characterized by repeated genomic segments, contributes to the chromosomal rearrangements around PLP1 and the manifestation of PMD. Thus, PMD is recognized as a chromosomal disorder.
authors.affiliation: Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan. yamamoto.toshiyuki@twmu.ac.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
mesh_terms: D041321:Chromosomes, Human, X; D005260:Female; D020440:Gene Duplication; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D018991:Myelin Proteolipid Protein / Q000235:genetics; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics*; D010641:Phenotype
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human