Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha-mannosidosis.
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.
Sbaragli
Michele
M
Dipartimento di Medicina Interna, Università degli Studi di Perugia, Perugia, Italy.
Bibi
Lucia
L
Pittis
Maria Gabriela
MG
Balducci
Chiara
C
Heikinheimo
Pirkko
P
Ricci
Roberta
R
Antuzzi
Daniela
D
Parini
Rossella
R
Spaccini
Luigina
L
Bembi
Bruno
B
Beccari
Tommaso
T
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*
D018389:Codon, Nonsense; D011993:Recombinant Fusion Proteins; D043323:alpha-Mannosidase