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.
© 2012 The Authors. Congenital Anomalies © 2012 Japanese Teratology Society.