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Database: PubMed
Entry: 14974081
LinkDB: 14974081
Original site: 14974081 
PMID:
     14974081
Authors:
     Karageorgos L, Harmatz P, Simon J, Pollard A, Clements PR, Brooks DA,
     Hopwood JJ.
Title:
     Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial 
     of enzyme replacement therapy.
Journal:
     Hum Mutat. 2004 Mar;23(3):229-33. doi: 10.1002/humu.10313.
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.

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