Please use this identifier to cite or link to this item: http://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
RMID: 0020040220
DOI: 10.1002/humu.10313
Appears in Collections:Paediatrics publications

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