RESUMO
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.
Assuntos
Mutação Puntual , alfa-Manosidase/genética , alfa-Manosidose/genética , Animais , Catálise , Gatos , Bovinos , Linhagem Celular , Códon sem Sentido , Consanguinidade , Análise Mutacional de DNA , Humanos , Itália , Rim , Lisossomos/enzimologia , Camundongos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase , Conformação Proteica , Dobramento de Proteína , Proteínas Recombinantes de Fusão/metabolismo , Especificidade da Espécie , alfa-Manosidase/química , alfa-Manosidase/deficiência , alfa-Manosidase/metabolismo , alfa-Manosidose/classificação , alfa-Manosidose/enzimologiaRESUMO
The term dysostosis multiplex is specifically applied to the group of radiological features collectively found in a number of specific metabolic disorders including the mucopolysaccharidoses, mucolipidosis, mannosidosis, fucosidosis and several other rarer conditions. We report eight cases of mannosidosis, fucosidosis and mucolipidosis with special emphasis on the differentiation from the more common mucopolysaccharidoses.
