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Type: Journal article
Title: Identification, expression, and biochemical characterization of N-acetylgalactosamine-4-sulfatase mutations and relationship with clinical phenotype in MPS-VI patients
Author: Litjens, T.
Brooks, D.
Peters, C.
Gibson, G.
Hopwood, J.
Citation: American Journal of Human Genetics, 1996; 58(6):1127-1134
Publisher: CELL PRESS
Issue Date: 1996
ISSN: 0002-9297
Abstract: Maroteaux-Lamy syndrome, or mucopolysaccharidosis type VI (MPS-VI), is a lysosomal storage disorder characterized by the defective degradation of dermatan sulfate due to the deficiency of N-acetylgalactosamine-4-sulfatase (4S). The clinical severity of MPS-VI ranges in a continuum from mildly affected to severely affected patients. Mutations in MPS-VI patient samples were identified by chemical cleavage and direct DNA sequencing of PCR products derived from patient cDNA. Five amino acid substitutions were identified (T92M, R95Q, Y210C, H393P, and L498P), individually introduced into the wild-type 4S cDNA by site-directed in vitro mutagenesis, and transfected into Chinese hamster ovary cells. Three of the five mutations (R95Q, Y210C, and H393P) were observed in >1 of 25 unrelated MPS-VI patients; however, the mutations were not found in 20 control individuals. The residual 4S activity and protein (biochemical phenotype) were determined for each mutant in order to confirm their identity as mutations and to dissect the contribution of each mutant allele to the overall clinical phenotype of the patient. For each patient, the combined biochemical phenotypes of the two 4S mutant alleles demonstrated a good correspondence with the observed clinical phenotype (with the possible exception of a patient who was a compound heterozygote for T92M and L498P). This preliminary correspondence between genotype and the phenotype in MPS-VI may, with further refinement, contribute to the assessment of therapeutic approaches for MPS-VI patients.
Keywords: CHO Cells
Mucopolysaccharidosis VI
Recombinant Proteins
DNA, Complementary
DNA Primers
Restriction Mapping
Mutagenesis, Site-Directed
Polymerase Chain Reaction
Base Sequence
Point Mutation
Molecular Sequence Data
Child, Preschool
Appears in Collections:Aurora harvest
Paediatrics publications

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