1. Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha-mannosidosis.
- Author
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Sbaragli M, Bibi L, Pittis MG, Balducci C, Heikinheimo P, Ricci R, Antuzzi D, Parini R, Spaccini L, Bembi B, and Beccari T
- Subjects
- 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, Polymerase Chain Reaction, Protein Conformation, Protein Folding, Recombinant Fusion Proteins metabolism, Species Specificity, alpha-Mannosidase chemistry, alpha-Mannosidase deficiency, alpha-Mannosidase metabolism, alpha-Mannosidosis classification, alpha-Mannosidosis enzymology, Point Mutation, alpha-Mannosidase genetics, alpha-Mannosidosis genetics
- Abstract
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., ((c) 2005 Wiley-Liss, Inc.)
- Published
- 2005
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