title: Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia.
abstract: OBJECTIVE
  Congenital disorders of glycosylation (CDG) result from mutations in N-glycan biosynthesis. Mutations in phosphomannomutase (PMM2) cause CDG-Ia. Here, we report four clinically mild patients and their mutations in PMM2.
  
  
  METHODS
  Analysis of the PMM2 cDNA and gene revealed the mutations affecting the glycosylation efficiency.
  
  
  RESULTS
  The patients have 30% to 50% normal PMM activity in fibroblasts due to different mutations in PMM2, and we studied the effect of each mutation on the PMM activity in a Saccharomyces cerevisiae expression system.
  
  
  CONCLUSIONS
  Each patient carried a severe mutation that decreased the PMM activity to less than 10% as well as a relatively mild mutation. A new mutation, deletion of base 24, changed the reading frame. The C9Y, C241S, and L32R mutations showed 27% to 45% activity when expressed in the eukaryotic expression system, and the more severe D148N was shown to be thermolabile.
authors.affiliation: The Burnham Institute, Glycobiology Program, La Jolla, California 92037, USA.
authors.forename: V
authors.initials: V
authors.lastname: Westphal
authors.forename: S
authors.initials: S
authors.lastname: Peterson
authors.forename: M
authors.initials: M
authors.lastname: Patterson
authors.forename: A
authors.initials: A
authors.lastname: Tournay
authors.forename: A
authors.initials: A
authors.lastname: Blumenthal
authors.forename: E P
authors.initials: EP
authors.lastname: Treacy
authors.forename: H H
authors.initials: HH
authors.lastname: Freeze
mesh_terms: D000483:Alleles; D002648:Child; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D008297:Male; D009154:Mutation; D009679:Nuclear Family; D010375:Pedigree; D010641:Phenotype; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics* / Q000378:metabolism; D016364:Reading Frames; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012867:Skin / Q000166:cytology
chemical_list: D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase