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https://hdl.handle.net/2440/7361
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Type: | Journal article |
Title: | Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial of enzyme replacement therapy |
Author: | Karageorgos, L. Harmatz, P. Simon, J. Pollard, A. Clements, P. Brooks, D. Hopwood, J. |
Citation: | Human Mutation, 2004; 23(3):229-233 |
Publisher: | Wiley-Liss |
Issue Date: | 2004 |
ISSN: | 1059-7794 1098-1004 |
Abstract: | Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB). Seven MPS VI patients were chosen for the initial clinical trial of enzyme replacement therapy. Direct sequencing of genomic DNA from these patients was used to identify ARSB mutations. Each individual exon of the ARSB gene was amplified by PCR and subsequently sequenced. Nine substitutions (c.289C>T [p.Q97X], c.629A>G [p.Y210C], c.707T>C [p.L236P], c.936G>T [p.W312C], c.944G>A [p.R315Q], c.962T>C [p.L321P], c.979C>T [p.R327X], c.1151G>A [p.S384N], and c.1450A>G [p.R484G]), two deletions (c.356_358delTAC [p.Y86del] and c.427delG), and one intronic mutation (c.1336+2T>G) were identified. A total of 7 out of the 12 mutations identified were novel (p.Y86del, p.Q97X, p.W312C, p.R327X, c.427delG, p.R484G, and c.1336+2T>G). Two of these novel mutations (p.Y86del and p.W312C) were expressed in Chinese hamster ovary cells and analyzed for residual ARSB activity and mutant ARSB protein. The two common polymorphisms c.1072G>A [p.V358M] and c.1126G>A [p.V376M] were identified among the patients, along with the silent mutation c.1191A>G. Cultured fibroblast ARSB mutant protein and residual activity were determined for each patient, and, together with genotype information, were used to predict the expected clinical severity of each MPS VI patient. |
Keywords: | Cells, Cultured Cell Line CHO Cells Fibroblasts Skin Animals Humans Mucopolysaccharidosis IV N-Acetylgalactosamine-4-Sulfatase DNA Mutational Analysis Alternative Splicing Sequence Deletion Mutation, Missense Point Mutation Introns Cricetinae |
DOI: | 10.1002/humu.10313 |
Published version: | http://dx.doi.org/10.1002/humu.10313 |
Appears in Collections: | Aurora harvest Paediatrics publications |
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