Remarkably, mutations inducing a complete arrest of PLP/DM20 trafficking in the ER are associated with the most severe form of the disease and with oligodendrocyte death (connatal PMD), whereas mutations resulting in a partial block of PLP and/or DM20 trafficking are associated with milder disease phenotype (classical PMD) (Gow and Lazzarini, 1996; Southwood and Gow, 2001). Here, PLP1 is linked to Pelizeaus-Merzbacher spectrum disorder.