Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha-mannosidosis

Hum Mutat. 2005 Mar;25(3):320. doi: 10.1002/humu.9310.


Mutation analysis performed on six Italian families with alpha-mannosidosis type II allowed the identification of five new mutations in the MAN2B1 gene: c.157G>T, c.562C>T, c.599A>T, c.293dupA, c.2402G>A (p.E53X, p.R188X, p.H200L, p.Y99VfsX61, p.G801D). Protein residues G801 and H200 are conserved among the four mammalian alpha-mannosidases cloned to date: human, cattle, cat and mouse. In vitro expression studies demonstrated that both missense mutations expressed no residual alpha-mannosidase activity indicating that they are disease-causing mutations. Modelling into the three-dimensional structure revealed that the p.H200L could involve the catalytic mechanism, whereas p.G801D would affect the correct folding of the enzyme.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalysis
  • Cats
  • Cattle
  • Cell Line
  • Codon, Nonsense
  • Consanguinity
  • DNA Mutational Analysis
  • Humans
  • Italy
  • Kidney
  • Lysosomes / enzymology
  • Mice
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutation, Missense
  • Point Mutation*
  • Polymerase Chain Reaction
  • Protein Conformation
  • Protein Folding
  • Recombinant Fusion Proteins / metabolism
  • Species Specificity
  • alpha-Mannosidase / chemistry
  • alpha-Mannosidase / deficiency
  • alpha-Mannosidase / genetics*
  • alpha-Mannosidase / metabolism
  • alpha-Mannosidosis / classification
  • alpha-Mannosidosis / enzymology
  • alpha-Mannosidosis / genetics*


  • Codon, Nonsense
  • Recombinant Fusion Proteins
  • alpha-Mannosidase

Associated data

  • OMIM/248500