BACKGROUND: Mucopolysaccharidosis type I (MPS I) patients present a wide range of clinical manifestations, which could be due to the high molecular heterogeneity of the IDUA gene and to pathological events besides the enzyme deficiency. The aim of this study was to identify the most common MPS I causing mutations and to evaluate some oxidative stress markers in Brazilian patients. METHODS: 3 common mutations in the IDUA gene were searched in 11 MPS I patients by PCR-RFLP. Activities of antioxidant enzymes catalase and superoxide dismutase, and levels of total glutathione and thiobarbituric acid reactive substances were evaluated by spectrophotometric and colorimetric methods, during different periods of enzyme replacement therapy. RESULTS: The most common mutations were P533R and W402X, with allelic frequencies of 33.33% and 27.8% respectively. MPS I patients presented high levels of lipid peroxidation and enzyme replacement therapy led to an increase of catalase and a decrease of superoxide dismutase activities. CONCLUSIONS: P533R and W402X accounted for more than 60% of the alleles, but no genotype-phenotype correlation could be established. The alterations in antioxidant enzyme activities suggest that oxidative stress may be an important event among MPS I patients, which could contribute to the physiopathology of the disease.
BACKGROUND:Mucopolysaccharidosis type I (MPS I) patients present a wide range of clinical manifestations, which could be due to the high molecular heterogeneity of the IDUA gene and to pathological events besides the enzyme deficiency. The aim of this study was to identify the most common MPS I causing mutations and to evaluate some oxidative stress markers in Brazilian patients. METHODS: 3 common mutations in the IDUA gene were searched in 11 MPS Ipatients by PCR-RFLP. Activities of antioxidant enzymes catalase and superoxide dismutase, and levels of total glutathione and thiobarbituric acid reactive substances were evaluated by spectrophotometric and colorimetric methods, during different periods of enzyme replacement therapy. RESULTS: The most common mutations were P533R and W402X, with allelic frequencies of 33.33% and 27.8% respectively. MPS Ipatients presented high levels of lipid peroxidation and enzyme replacement therapy led to an increase of catalase and a decrease of superoxide dismutase activities. CONCLUSIONS:P533R and W402X accounted for more than 60% of the alleles, but no genotype-phenotype correlation could be established. The alterations in antioxidant enzyme activities suggest that oxidative stress may be an important event among MPS Ipatients, which could contribute to the physiopathology of the disease.
Authors: Elsa G Shapiro; Igor Nestrasil; Kyle Rudser; Kathleen Delaney; Victor Kovac; Alia Ahmed; Brianna Yund; Paul J Orchard; Julie Eisengart; Gregory R Niklason; Julian Raiman; Eva Mamak; Morton J Cowan; Mara Bailey-Olson; Paul Harmatz; Suma P Shankar; Stephanie Cagle; Nadia Ali; Robert D Steiner; Jeffrey Wozniak; Kelvin O Lim; Chester B Whitley Journal: Mol Genet Metab Date: 2015-06-17 Impact factor: 4.797
Authors: Roberto Giugliani; Andressa Federhen; Maria Verônica Muñoz Rojas; Taiane Vieira; Osvaldo Artigalás; Louise Lapagesse Pinto; Ana Cecília Azevedo; Angelina Acosta; Carmen Bonfim; Charles Marques Lourenço; Chong Ae Kim; Dafne Horovitz; Denize Bonfim; Denise Norato; Diane Marinho; Durval Palhares; Emerson Santana Santos; Erlane Ribeiro; Eugênia Valadares; Fábio Guarany; Gisele Rosone de Lucca; Helena Pimentel; Isabel Neves de Souza; Jordão Correa; José Carlos Fraga; José Eduardo Goes; José Maria Cabral; José Simionato; Juan Llerena; Laura Jardim; Liane Giuliani; Luiz Carlos Santana da Silva; Mara L Santos; Maria Angela Moreira; Marcelo Kerstenetzky; Márcia Ribeiro; Nicole Ruas; Patricia Barrios; Paulo Aranda; Rachel Honjo; Raquel Boy; Ronaldo Costa; Carolina Souza; Flavio F Alcantara; Silvio Gilberto A Avilla; Simone Fagondes; Ana Maria Martins Journal: Genet Mol Biol Date: 2010-12-01 Impact factor: 1.771
Authors: Alzbeta Vazna; Clare Beesley; Linda Berna; Larisa Stolnaja; Helena Myskova; Michaela Bouckova; Hana Vlaskova; Helena Poupetova; Jiri Zeman; Martin Magner; Anna Hlavata; Bryan Winchester; Martin Hrebicek; Lenka Dvorakova Journal: Am J Med Genet A Date: 2009-05 Impact factor: 2.802