کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10833659 | 1065805 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Residual α-l-iduronidase activity in fibroblasts of mild to severe Mucopolysaccharidosis type I patients
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کلمات کلیدی
ScheieMPS IH4MU4-methylumbelliferoneIDUAα-L-iduronidaseHSCTEnzyme-replacement therapy - آنزیم جایگزین درمانScheie syndrome - سندرم شرمHurler syndrome - سندرم هورلرNewborn screening - غربالگری نوزادانResidual activity - فعالیت باقیماندهMucopolysaccharidosis - موکوپلیساکاریدوزMPs - نمایندگان مجلسERT - هستندHurler - هورلرHematopoietic stem cell transplantation - پیوند مغز استخوان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Three major clinical subgroups are usually distinguished in Mucopolysaccharidosis type I: Hurler (MPS IH, severe presentation), Hurler-Scheie (MPS IH/S, intermediate) and Scheie (MPS IS, mild). To facilitate treatment with hematopoietic stem-cell transplantation, early diagnosis is important for MPS IH patients. Although screening for MPS I in newborns would allow detection at an early age, it may be difficult to predict the phenotype on the basis of the genotype in these infants. Extra diagnostic tools are thus required. Based on the hypothesis that distinct MPS I phenotypes may result from differences in residual α-l-iduronidase (IDUA) activity, we modified the common IDUA assay using the substrate 4-methylumbelliferyl-α-l-iduronide to allow quantification of low IDUA activity in MPS I fibroblasts. Enzyme incubation was performed with high protein concentrations at different time points up to 8 h. Mean residual IDUA activity was 0.18% (range 0-0.6) of the control value in MPS IH fibroblasts (n = 5); against 0.27% (range 0.2-0.3) in MPS IH/S cells (n = 3); and 0.79% (range 0.3-1.8) in MPS IS fibroblasts (n = 5). These results suggest that residual IDUA activity and severity of the MPS I phenotype are correlated. Two MPS IS patients with rare (E276K/E276K) or indefinite (A327P/unknown) IDUA genotypes had residual IDUA activity in the MPS IS range, illustrating the usefulness of our approach. IDUAE276K was very unstable at 37 °C, but more stable at 23 °C, suggesting thermal instability. We conclude that this procedure for determining residual IDUA activity in fibroblasts of MPS I patients may be helpful to predict MPS I phenotype.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 109, Issue 4, August 2013, Pages 377-381
Journal: Molecular Genetics and Metabolism - Volume 109, Issue 4, August 2013, Pages 377-381
نویسندگان
Esmee Oussoren, Joke Keulemans, Otto P. van Diggelen, Linda F. Oemardien, Remco G. Timmermans, Ans T. van der Ploeg, George J.G. Ruijter,