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Type: Journal article
Title: Mutational analysis of mucopolysaccharidosis type VI patients undergoing a phase II trial of enzyme replacement therapy
Author: Karageorgos, L.
Brooks, D.
Harmatz, P.
Ketteridge, D.
Pollard, A.
Melville, E.
Parkinson-Lawrence, E.
Clements, P.
Hopwood, J.
Citation: Molecular Genetics and Metabolism, 2007; 90(2):164-170
Publisher: Academic Press Inc Elsevier Science
Issue Date: 2007
ISSN: 1096-7192
Statement of
Litsa Karageorgos, Doug A. Brooks, Paul Harmatz, David Ketteridge, Anthony Pollard, Elizabeth L. Melville, Emma Parkinson-Lawrence, Peter R. Clements and John J. Hopwood
Abstract: Mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome) is a lysosomal storage disorder caused by mutations in the N-acetylgalactosamine-4-sulfatase (ARSB) gene. These mutations result in a deficiency of ARSB activity. Ten MPS VI patients were involved in a phase II clinical study 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. Thirteen substitutions (c.215T>G [p.L72R] c.284G>A [p.R95Q], c.305G>A [p.R102H], c.323G>T [p.G108V], c.389C>T [p.P130L], c.511G>A [p.G171S], c.904G>A [p.G302R], c.944G>A [p.R315Q], c.1057T>C [p.W353R], c.1151G>A [p.S384N], c.1178A>C [p.H393P], c.1289A>G [p.H430R] and c.1336G>C [p.G446R]), one deletion (c.238delG), and two intronic mutations (c.1213+5G>A and c.1214-2A>G) were identified. Nine of the 16 mutations identified were novel (R102H, G108V, P130L, G171S, W353R, H430R, G446R, c.1213+5G>A and c.1214-2A>G). The two common polymorphisms c.1072G>A [p.V358M] and c.1126G>A [p.V376M] were identified in some of the patients, along with the silent mutations c.972A>G and c.1191A>G. Cultured fibroblast ARSB mutant protein and residual activity were determined for each patient and, together with genotype information, used to predict the expected clinical severity of each patient.
Keywords: Humans; Mucopolysaccharidosis IV; N-Acetylgalactosamine-4-Sulfatase; Recombinant Proteins; DNA Mutational Analysis; Mutation; Adolescent; Adult; Child; Female; Male
Description: Copyright © 2006 Elsevier Inc. All rights reserved.
RMID: 0020070264
DOI: 10.1016/j.ymgme.2006.10.008
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Appears in Collections:Paediatrics publications

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