title: beta-Glucuronidase P408S, P415L mutations: evidence that both mutations combine to produce an MPS VII allele in certain Mexican patients.
abstract: Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is an autosomal recessively inherited lysosomal storage disease caused by a deficiency in beta-glucuronidase. We identified and studied a novel allele containing two C-to-T transitions resulting in P408S and P415L alterations, which is present in homozygous state in one Mexican patient and in heterozygous state in another. None of the previous reports describing mutations in the MPS VII gene include Mexican patients. Expression of either of the mutations individually showed only modest effects on the properties of the enzyme. However, expression of the doubly mutant allele resulted in markedly reduced activity and rapid degradation in an early biosynthetic compartment.
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University Health Sciences Center, MO 63104, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Islam
authors.forename: R
authors.initials: R
authors.lastname: Vervoort
authors.forename: W
authors.initials: W
authors.lastname: Lissens
authors.forename: J J
authors.initials: JJ
authors.lastname: Hoo
authors.forename: L A
authors.initials: LA
authors.lastname: Valentino
authors.forename: W S
authors.initials: WS
authors.lastname: Sly
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005260:Female; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008800:Mexico; D008969:Molecular Sequence Data; D016538:Mucopolysaccharidosis VII / Q000208:ethnology / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D017931:DNA Primers; D005966:Glucuronidase