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Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha‐mannosidosis
Author(s) -
Sbaragli Michele,
Bibi Lucia,
Pittis Maria Gabriela,
Balducci Chiara,
Heikinheimo Pirkko,
Ricci Roberta,
Antuzzi Daniela,
Parini Rossella,
Spaccini Luigina,
Bembi Bruno,
Beccari Tommaso
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9310
Subject(s) - missense mutation , biology , mutation , microbiology and biotechnology , genetics , gene , alpha (finance) , medicine , construct validity , nursing , patient satisfaction
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. © 2005 Wiley‐Liss, Inc.