Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/44389
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Type: Journal article
Title: Mutational analysis of 105 mucopolysaccharidosis type VI patients
Author: Karageorgos, L.
Brooks, D.
Pollard, A.
Melville, E.
Hein, L.
Clements, P.
Ketteridge, D.
Swiedler, S.
Beck, M.
Giugliani, R.
Harmatz, P.
Wraith, J.
Guffon, N.
Teles, E.
Miranda, C.
Hopwood, J.
Citation: Human Mutation, 2007; 28(9):897-903
Publisher: Wiley-Liss
Issue Date: 2007
ISSN: 1059-7794
1098-1004
Statement of
Responsibility: 
Litsa Karageorgos, Doug A. Brooks, Anthony Pollard, Elizabeth L. Melville, Leanne K. Hein, Peter R. Clements, David Ketteridge, Stuart J. Swiedler, Michael Beck, Roberto Giugliani, Paul Harmatz, James E. Wraith, Nathalie Guffon, Elisa Leão Teles, M. Clara Sá Miranda, 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 (arylsulfatase B, ARSB) gene. ARSB is a lysosomal enzyme involved in the degradation of the glycosaminoglycans (GAG) dermatan and chondroitin sulfate. ARSB mutations reduce enzyme function and GAG degradation, causing lysosomal storage and urinary excretion of these partially degraded substrates. Disease onset and rate of progression is variable, producing a spectrum of clinical presentation. In this study, 105 MPS VI patients-representing about 10% of the world MPS VI population-were studied for molecular genetic and biochemical parameters. Direct sequencing of patient genomic DNA was used to identify ARSB mutations. In total, 83 different disease-causing mutations were found, 62 of which were previously unknown. The novel sequence changes included: 38 missense mutations, five nonsense mutations, 11 deletions, one insertion, seven splice-site mutations, and four polymorphisms. ARSB mutant protein and residual activity were determined on fibroblast extracts for each patient. The identification of many novel mutations unique to individuals/their families highlighted the genetic heterogeneity of the disorder and provided an appropriate cohort to study the MPS VI phenotypic spectrum. This mutation analysis has identified a clear correlation between genotype and urinary GAG that can be used to predict clinical outcome.
Keywords: mucopolysaccharidosis type VI; MPS VI; Maroteaux-Lamy; arylsulfatase B; ARSB
Rights: Copyright © 2007 Wiley-Liss, Inc
RMID: 0020072378
DOI: 10.1002/humu.20534
Published version: http://www3.interscience.wiley.com/journal/114220914/abstract
Appears in Collections:Paediatrics publications

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