Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/89649
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Type: Book chapter
Title: Aminoglycoside-induced premature stop codon read-through of mucopolysaccharidosis type I patient Q70X and W402X mutations in cultured cells
Author: Kamei, M.
Kasperski, K.
Fuller, M.
Parkinson-Lawrence, E.
Karageorgos, L.
Belakhov, V.
Baasov, T.
Hopwood, J.
Brooks, D.
Citation: JIMD Reports - Case and Research Reports, Volume 13, 2014 / Zschocke, J., Gibson, K., BRown, G., Morava, E., Peters, V. (ed./s), Ch.18, pp.139-147
Publisher: Springer
Publisher Place: Heidelberg
Issue Date: 2014
ISBN: 9783642541490
Statement of
Responsibility: 
Makoto Kamei, Karissa Kasperski, Maria Fuller, Emma J. Parkinson-Lawrence, Litsa Karageorgos, Valery Belakhov, Timor Baasov, John J. Hopwood, Doug A. Brooks
Abstract: The premature stop codon mutations, Q70X and W402X, are the most common α-l-iduronidase gene (IDUA) mutations in mucopolysaccharidosis type I (MPS I) patients. Read-through drugs have been used to suppress premature stop codons, and this can potentially be used to treat patients who have this type of mutation. We examined the effects of aminoglycoside treatment on the IDUA mutations Q70X and W402X in cultured cells and show that 4,5-disubstituted aminoglycosides induced more read-through for the W402X mutation, while 4,6-disubstituted aminoglycosides promoted more read-through for the Q70X mutation: lividomycin (4,5-disubstituted) induced a 7.8-fold increase in α-l-iduronidase enzyme activity for the W402X mutation; NB54 (4,5-disubstituted) induced a 3.7 fold increase in the amount of α-l-iduronidase enzyme activity for the W402X mutation, but had less effect on the Q70X mutation, whereas gentamicin (4,6-disubstituted) had the reverse effect on read-through for both mutations. The predicted mRNA secondary structural changes for both mutations were markedly different, which may explain these different effects on read-through for these two premature stop codons.
Description: Series: JIMD Reports, 2192-8304 ; 13
Rights: © SSIEM and Springer-Verlag Berlin Heidelberg 2013
RMID: 0020134141
DOI: 10.1007/8904_2013_270
Grant ID: http://purl.org/au-research/grants/nhmrc/511321
Appears in Collections:Paediatrics publications

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