title: Mutational analysis in longest known survivor of mucopolysaccharidosis type VII.
abstract: Mucopolysaccharidosis VII (MPS VII) is an autosomal recessive disorder caused by the deficiency of beta-glucuronidase leading to the intralysosomal storage of heparan, dermatan, and chondroitin sulfate. Here, we report the identification of two novel missense mutations K350N and R577L in a 37-year-old patient with beta-glucuronidase deficiency and a relatively mild MPS VII phenotype. Expression of the K350N mutation in baby hamster kidney cells has revealed residual enzymatic activity and normal transport of the enzyme to the lysosome. However, expression of the R577L or the double mutant K350N/R577L results in rapid degradation of the enzyme in early biosynthetic compartments and a total loss of enzymatic activity. We attribute the mild phenotype to the residual catalytic activity provided by the K350N mutant. At the time of her death at the age of 37 years, this patient was the longest known survivor with MPS VII.
authors.affiliation: UKE-University Hospital, Children's Hospital, University of Hamburg, Martinistrasse 52, Haus W23, 20246 Hamburg, Germany. storch@uke.uni-hamburg.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Storch
authors.forename: Birgit
authors.initials: B
authors.lastname: Wittenstein
authors.forename: Rafiqul
authors.initials: R
authors.lastname: Islam
authors.forename: Kurt
authors.initials: K
authors.lastname: Ullrich
authors.forename: William S
authors.initials: WS
authors.lastname: Sly
authors.forename: Thomas
authors.initials: T
authors.lastname: Braulke
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006224:Cricetinae; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004285:Dogs; D004795:Enzyme Stability; D005260:Female; D005966:Glucuronidase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000201:enzymology; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D016538:Mucopolysaccharidosis VII / Q000201:enzymology / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D051381:Rats; D017741:Survivors; D014162:Transfection
chemical_list: D017931:DNA Primers; D008715:Methionine; D005966:Glucuronidase