DPM2-CDG: a muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy

Ann Neurol. 2012 Oct;72(4):550-8. doi: 10.1002/ana.23632.


Objective: Congenital disorders of glycosylation (CDG) are a group of metabolic diseases due to defects in protein and lipid glycosylation. We searched for the primary defect in 3 children from 2 families with a severe neurological phenotype, including profound developmental delay, intractable epilepsy, progressive microcephaly, severe hypotonia with elevated blood creatine kinase levels, and early fatal outcome. There was clinical evidence of a muscular dystrophy-dystroglycanopathy syndrome, supported by deficient O-mannosylation by muscle immunohistochemistry.

Methods: Biochemical and molecular methods were combined to pinpoint the defect in the glycosylation pathway in the endoplasmic reticulum.

Results: Metabolic investigations revealed CDG-I, pointing to a defect in protein N-glycosylation in the endoplasmic reticulum. Analysis of lipid-linked oligosaccharides in fibroblasts showed accumulation of Dol-PP-GlcNAc(2) -Man(5) . DNA analysis revealed mutations in DPM2, 1 of the subunits of the dolichol-phosphate-mannose (DPM) synthase; the patient in the first family is compound heterozygous for 2 mutations (c.68A>G, predicting a missense mutation p.Y23C and c.4-1G>C, a splice mutation), whereas the patients in the second family are homozygous for the same missense mutation (c.68A>G, p.Y23C).

Interpretation: We describe a new CDG, due to a deficiency of DPM2. Hence, mutations have now been described in the genes for the 3 subunits of DPM: DPM1, DPM2, and DPM3, whereby DPM2-CDG links the congenital disorders of glycosylation to the congenital muscular dystrophies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Coagulation Protein Disorders / genetics
  • Congenital Disorders of Glycosylation / complications
  • Congenital Disorders of Glycosylation / genetics*
  • DNA Mutational Analysis
  • Drug Resistance
  • Dystroglycans / metabolism
  • Electromyography
  • Endoplasmic Reticulum
  • Epilepsy / etiology
  • Epilepsy / genetics*
  • Female
  • Fibroblasts / metabolism
  • Glycosylation
  • Humans
  • Infant
  • Isoelectric Focusing
  • Liver Diseases / complications
  • Liver Diseases / genetics
  • Male
  • Mannose / metabolism
  • Mannosyltransferases / genetics*
  • Microcephaly / genetics
  • Microcephaly / pathology
  • Middle Aged
  • Molecular Sequence Data
  • Muscular Dystrophies / complications
  • Muscular Dystrophies / genetics*
  • Mutation / genetics
  • Mutation / physiology
  • Mutation, Missense / genetics
  • Mutation, Missense / physiology
  • Pregnancy
  • Vision Disorders / genetics
  • Vision Disorders / pathology
  • Young Adult


  • Dystroglycans
  • DPM2 protein, human
  • Mannosyltransferases
  • Mannose