دورية أكاديمية
a-L-iduronidase premature stop codons and potential read-through in mucopolysaccharidosis type I patients
| العنوان: | a-L-iduronidase premature stop codons and potential read-through in mucopolysaccharidosis type I patients |
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| المؤلفون: | Hein, L., Bawden, M., Muller, V., Sillence, D., Hopwood, J., Brooks, D. |
| بيانات النشر: | Academic Press Ltd Elsevier Science Ltd |
| سنة النشر: | 2004 |
| المجموعة: | The University of Adelaide: Digital Library |
| مصطلحات موضوعية: | α-l-iduronidase, Hurler syndrome, mucopolysaccharidosis type I, stop codons, read-through |
| الوصف: | α-l-Iduronidase is a glycosyl hydrolase involved in the sequential degradation of the glycosaminoglycans heparan sulphate and dermatan sulphate. A deficiency in α-l-iduronidase results in the lysosomal accumulation and urinary secretion of partially degraded glycosaminoglycans and is the cause of the lysosomal storage disorder mucopolysaccharidosis type I (MPS I; Hurler and Scheie syndromes; McKusick 25280). The premature stop codons Q70X and W402X are two of the most common α-l-iduronidase gene (IDUA) mutations accounting for up to 70% of MPS I disease alleles in some populations. Here, we have reported a new mutation, making a total of 15 different mutations that can cause premature IDUA stop codons and have investigated the biochemistry of these mutations. Natural stop codon read-through was dependent on the fidelity of the codon when evaluated at Q70X and W402X in CHO-K1 cells, but the three possible stop codons TAA, TAG and TGA, had different effects on mRNA stability and this effect was context dependent. In CHO-K1 cells expressing the Q70X and W402X mutations, the level of gentamicin-enhanced stop codon read-through was slightly less than the increment in activity caused by a lower fidelity stop codon. In this system, gentamicin had more effect on read-through for the TAA and TGA stop codons when compared to the TAG stop codon. In an MPS I patient study, premature TGA stop codons were associated with a slightly attenuated clinical phenotype, when compared to classical Hurler syndrome (e.g. W402X/W402X and Q70X/Q70X genotypes with TAG stop codons). Natural read-through of premature stop codons is a potential explanation for variable clinical phenotype in MPS I patients. Enhanced stop codon read-through is a potential treatment strategy for a large sub-group of MPS I patients. ; Leanne K Hein, Michael Bawden, Vivienne J Muller, David Sillence, John J Hopwood and Doug A Brooks |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0022-2836 1089-8638 |
| العلاقة: | Journal of Molecular Biology, 2004; 338(3):453-462; http://hdl.handle.net/2440/7539Test; Brooks, D. [0000-0001-9098-3626] |
| DOI: | 10.1016/j.jmb.2004.03.012 |
| الإتاحة: | https://doi.org/10.1016/j.jmb.2004.03.012Test http://hdl.handle.net/2440/7539Test |
| رقم الانضمام: | edsbas.8202B586 |
| قاعدة البيانات: | BASE |
| تدمد: | 00222836 10898638 |
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| DOI: | 10.1016/j.jmb.2004.03.012 |