DPM2-CDG is an autosomal recessive disorder caused by pathogenic variants in dolichyl-phosphate mannosyltransferase polypeptide 2, regulatory subunit gene (DPM2), coding for DPM2 protein. DPM2 is part of the dolichol-phosphate-mannose synthase (DPMS) complex, which transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man). Hence, it is involved in N-glycosylation, O-linked glycosylation, and glycosylphosphatidylinositol (GPI)-anchor synthesis. DPMS is composed of DPM1, DPM2, and DPM3. DPM2, along with DPM3 protein has been described as a regulatory subunit of DPMS, while DPM1 has been characterized as a catalytic subunit. DPMS is directly linked to glycosylation by providing mannose to growing glycan chains. Given that DPM2 deficiency results in glycosylation abnormalities, the disorder was classified as DPM2-CDG. Only 4 individuals with DPM2-CDG have been described up to date. This disorder was previously described as lethal muscular dystrophy syndrome and hence might be underreported. The exact prevalence of DPM2-CDG is not known.
DPM2