Position effect on PLP1 may cause a subset of Pelizaeus-Merzbacher disease symptoms

Abstract
We have mapped and analysed the chromosomal breakpoint regions of a male patient with an inv(X) (p22.3; q22) suffering from a subset of PMD symptoms including moderate mental retardation (Wechsler Intelligence Scale for Children, revised Dutch edition (WISC-RN) IQ 55–59) and cerebellar ataxia associated with dysmyelination. The breakage event in Xq22 affects GLRA4, a putative pseudogene of the glycine receptor gene family, approximately 70 kb apart from the PLP1 gene. We discuss the fact that a position effect on PLP1, rather than a duplication or missense mutation, is considered to be causative for a subset of clinical PMD symptoms.