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In Pelizaeus-Merzbacher disease, a myelination defect, a subgroup of mutations affecting the extracellular loop of the PLP/DM20 protein impair formation of intramolecular disulfide bridges and cause abnormal protein cross-links, ER retention and oligodendrocyte death (Dhaunchak et al., 2005) and von Willebrand disease (Wang et al., 2012)