title: Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha-mannosidosis.
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.
authors.affiliation: Dipartimento di Medicina Interna, Università degli Studi di Perugia, Perugia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Sbaragli
authors.forename: Lucia
authors.initials: L
authors.lastname: Bibi
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Pittis
authors.forename: Chiara
authors.initials: C
authors.lastname: Balducci
authors.forename: Pirkko
authors.initials: P
authors.lastname: Heikinheimo
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricci
authors.forename: Daniela
authors.initials: D
authors.lastname: Antuzzi
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.forename: Luigina
authors.initials: L
authors.lastname: Spaccini
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
authors.forename: Tommaso
authors.initials: T
authors.lastname: Beccari
mesh_terms: D000818:Animals; D002384:Catalysis; D002415:Cats; D002417:Cattle; D002460:Cell Line; D018389:Codon, Nonsense; D003241:Consanguinity; D004252:DNA Mutational Analysis; D006801:Humans; D007558:Italy; D007668:Kidney; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013045:Species Specificity; D043323:alpha-Mannosidase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008363:alpha-Mannosidosis / Q000145:classification / Q000201:enzymology / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D011993:Recombinant Fusion Proteins; D043323:alpha-Mannosidase