Minicircle DNA-based gene therapy coupled with immune modulation permits long-term expression of alpha-L-iduronidase in mice with mucopolysaccharidosis type I.
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A novel p.E276K IDUA mutation decreasing alpha-L-iduronidase activity causes mucopolysaccharidosis type I.
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PURPOSE: To characterize the pathogenic mutations causing mucopolysaccharidosis type I (MPS I) in two Thai patients: one with Hurler syndrome (MPS IH), the most severe form, and the other with Scheie syndrome (MPS IS), the mildest. Both presented with distinctive phenotype including corneal clouding. METHODS: The entire coding regions of the alpha-L-iduronidase (IDUA) gene were amplified by PCR and sequenced. Functional characterization of the mutant IDUA was determined by transient transfection of the construct into COS-7 cells. RESULTS: Mutation analyses revealed that the MPS IH patient was homozygous for a previously reported mutation, c.252insC, while the MPS IS patient was found to harbor a novel c.826G>A (p.E276K) mutation. The novel p.E276K mutation was not detected in 100 unaffected ethnic-matched control chromosomes. In addition, the glutamic acid residue at codon 276 was located at a well conserved residue. Transient transfection of the p.E276K construct revealed a significant reduction of IDUA activity compared to that of the wild-type IDUA suggesting it as a disease-causing mutation. CONCLUSIONS: This study reports a novel mutation, expanding the mutational spectrum for MPS I. (+info)
Arterial pathology in canine mucopolysaccharidosis-I and response to therapy.
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