title: Hyper-IgE syndromes: reviewing PGM3 deficiency.
abstract: OBJECTIVE
  The hyper-IgE syndromes have been recognized as a group of primary immunodeficiencies characterized by eczema, recurrent skin and lung infections, and elevated serum IgE. Recently, mutations in phosphoglucomutase 3 (encoding PGM3, which is involved in the protein glycosylation pathway) have been identified in autosomal recessive forms of hyper-IgE syndromes.
  
  
  RESULTS
  Autosomal recessive, hypomorphic PGM3 mutations cause a multisystem disorder, characterized by both a congenital glycosylation disease and a hyper-IgE syndrome. The reported mutations in PGM3 led to an impaired biosynthesis of UDP-GlcNAc and impaired tri-antennary and tetra-antennary N-glycan structures. Laboratory results in patients showed eosinophilia, a T-cell proliferation defect, and a reversed CD4/CD8 ratio. The impaired glycosylation in PGM3-mutant patients will not only affect proteins involved in the immune system, and thus causes a multisystem phenotype.
  
  
  CONCLUSIONS
  The identification of hyper-IgE syndromes-associated mutations in PGM3 provides the basis for future studies on the pathophysiology and the molecular mechanisms of eczema, IgE dysregulation, and increased susceptibility to infections.
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.forename: Manfred
authors.initials: M
authors.lastname: Fliegauf
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D002648:Child; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D007589:Job Syndrome / Q000235:genetics*; D010733:Phosphoglucomutase / Q000172:deficiency* / Q000235:genetics*
chemical_list: D007073:Immunoglobulin E; C549916:PGM3 protein, human; D010733:Phosphoglucomutase