title: Mucopolysaccharidosis VII in a Cat Caused by 2 Adjacent Missense Mutations in the GUSB Gene.
abstract: BACKGROUND
  Mucopolysaccharidoses (MPS) are common lysosomal storage disorders causing typically progressive skeletal and ocular abnormalities.
  
  
  OBJECTIVE
  To describe the clinic features, metabolic profile and a unique mutation in a domestic shorthair (DSH) kitten with MPS VII.
  
  
  METHODS
  Affected kitten and 80 healthy cats.
  
  
  METHODS
  Serum lysosomal enzyme activities and urinary glycosaminoglycan (GAG) accumulation were assessed. Exons of the β-glucuronidase gene (GUSB) were sequenced from genomic DNA and genotyping was conducted.
  
  
  RESULTS
  A 3-month-old DSH cat was presented for stunted growth, paresis, facial dysmorphia, multiple skeletal deformities, and corneal opacities. Evaluation of blood smears disclosed metachromatic granules in leukocytes and a urinary mucopolysaccharide spot test was positive. The proband had no GUSB activity but normal or increased activities for other lysosomal enzymes. Sequencing of the GUSB gene from the proband and comparison to the sequence of 2 healthy cats and the published feline genome sequence demonstrated 2 unique single base transitions (c.1421T>G and c.1424C>T) in exon 9, altering 2 adjacent codons (p.Ser475Ala and p.Arg476Trp). These amino acid changes are in a highly conserved domain of the GUSB protein and nontolerable to maintain function. Moreover, the p.Arg476Trp mutation previously has been identified in human patients. None of the other clinically healthy cats had these mutations.
  The diagnostic approach to MPS disorders is delineated. This is only the second mutation known to cause MPS VII in cats. Similarly, 2 different mutations have been described in MPS VII dogs, thereby showing the molecular heterogeneity of MPS VII in companion animals.
authors.affiliation: Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.affiliation: Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: J
authors.initials: J
authors.lastname: Sorenson
authors.affiliation: Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: S
authors.initials: S
authors.lastname: Strickland
authors.affiliation: Jordan Creek Animal Hospital, West Des Moines, IA.
authors.forename: C
authors.initials: C
authors.lastname: Mingus
authors.affiliation: Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: M E
authors.initials: ME
authors.lastname: Haskins
authors.affiliation: Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: U
authors.initials: U
authors.lastname: Giger
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000662:veterinary; D000818:Animals; D002371:Cat Diseases / Q000235:genetics*; D002415:Cats / Q000235:genetics; D005260:Female; D005796:Genes / Q000235:genetics; D005966:Glucuronidase / Q000235:genetics*; D016538:Mucopolysaccharidosis VII / Q000235:genetics / Q000662:veterinary*; D020125:Mutation, Missense / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000662:veterinary
chemical_list: D005966:Glucuronidase
keywords: Lysosomal storage disease; Ocular disease; Skeletal deformities; β-glucuronidase