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Most CDG are caused by defects in the N\u2010glycan biosynthesis, leading to multisystem phenotypes. However, the occurrence of tissue\u2010restricted clinical symptoms in the various defects in dolichol\u2010phosphate\u2010mannose (DPM) synthesis remains unexplained. To deepen our understanding of the tissue\u2010specific characteristics of defects in the DPM synthesis pathway, we investigated N\u2010glycosylation and O\u2010mannosylation in skeletal muscle of three DPM3\u2010CDG patients presenting with muscle dystrophy and hypo\u2010N\u2010glycosylation of serum transferrin in only two of them. In the three patients, O\u2010mannosylation of alpha\u2010dystroglycan (\u03b1DG) was strongly reduced and western blot analysis of beta\u2010dystroglycan (\u03b2DG) N\u2010glycosylation revealed a consistent lack of one N\u2010glycan in skeletal muscle. Recently, defective N\u2010glycosylation of \u03b2DG has been reported in patients with mutations in guanosine\u2010diphosphate\u2010mannose pyrophosphorylase B (<jats:italic>GMPPB<\/jats:italic>). Thus, we suggest that aberrant O\u2010glycosylation of \u03b1DG and N\u2010glycosylation of \u03b2DG in skeletal muscle is indicative of a defect in the DPM synthesis pathway. Further studies should address to what extent hypo\u2010N\u2010glycosylation of \u03b2DG or other skeletal muscle proteins contribute to the phenotype of patients with defects in DPM synthesis. Our findings contribute to our understanding of the tissue\u2010restricted phenotype of DPM3\u2010CDG and other defects in the DPM synthesis pathway.<\/jats:p>","DOI":"10.1002\/jimd.12095","type":"journal-article","created":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T02:19:38Z","timestamp":1554085178000},"page":"984-992","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Toward understanding tissue\u2010specific symptoms in dolichol\u2010phosphate\u2010mannose synthesis disorders; insight from DPM3\u2010CDG"],"prefix":"10.1002","volume":"42","author":[{"given":"Walinka","family":"van Tol","sequence":"first","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behavior Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences Radboud University 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