Molecular Characteristics

DPM2-CDG is caused by pathogenic variants in DPM2. Missense, non-sense and frameshift splicing type variants were reported. Genetic testing is the standard method to confirm DPM2-CDG diagnosis. Other complementary methods include DPMS enzymatic measurements. Glycosylation abnormalities can be screen by standard glycosylation analysis methods such as transferrin isoelectric focusing (TIEF), or MS based methods. DPM2 deficiency causes a disturbance of DPMS complex, which results in an inability to donate mannose to Dol-P. Dol-P-Man is essential in N-, O-glycosylation, and GPI-anchor synthesis and therefore, DPM2 deficiency causes glycosylation abnormalities.