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Mutational analysis of mucopolysaccharidosis type VI patients undergoing a phase II trial of enzyme replacement therapy
- Source :
- Molecular Genetics and Metabolism. 90:164-170
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
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.
- Subjects :
- Adult
Male
Arylsulfatase B
Silent mutation
Adolescent
N-Acetylgalactosamine-4-Sulfatase
Endocrinology, Diabetes and Metabolism
DNA Mutational Analysis
Mucopolysaccharidosis type VI
Biology
medicine.disease_cause
Biochemistry
Endocrinology
Genotype
Genetics
medicine
Humans
Child
Molecular Biology
Mutation
Mucopolysaccharidosis IV
Enzyme replacement therapy
medicine.disease
Molecular biology
Recombinant Proteins
Maroteaux–Lamy syndrome
Female
Subjects
Details
- ISSN :
- 10967192
- Volume :
- 90
- Database :
- OpenAIRE
- Journal :
- Molecular Genetics and Metabolism
- Accession number :
- edsair.doi.dedup.....c4d04b037320cc4f57e548fc47b6573e