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Mol Genet Metab ; 78(1): 37-43, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12559846

ABSTRACT

In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, alpha-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for alpha-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant alpha-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.


Subject(s)
Iduronidase/genetics , Mucopolysaccharidosis I/genetics , Animals , Blotting, Western , CHO Cells , Cricetinae , DNA/chemistry , DNA/genetics , DNA Mutational Analysis , Gene Expression Regulation, Enzymologic , Humans , Iduronidase/metabolism , Mucopolysaccharidosis I/enzymology , Mutation , Polymorphism, Single-Stranded Conformational , Transfection
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