title: Identification of a mutation causing mucopolysaccharidosis type IIIA in New Zealand Huntaway dogs.
abstract: Mucopolysaccharidosis type IIIA (MPS IIIA) is an autosomal recessive disease that occurs due to a deficiency of heparan sulfate sulfamidase (SGSH). The deficiency of SGSH results in the lysosomal accumulation and urinary excretion of the glycosaminoglycan heparan sulfate. The clinical severity of MPS IIIA is predominantly characterized by severe central nervous system degeneration. Naturally occurring MPS IIIA has recently been described in New Zealand Huntaway dogs, with similar disease progression and biochemical characteristics observed in severely affected MPS IIIA patients. Here, we identify the disease-causing mutation in the MPS IIIA Huntaway dog as 708-709insC. The frequency of the 708-709insC mutation in a sample group of 203 New Zealand Huntaway dogs was determined to be 3.8%. The identification of the 708-709insC mutation will permit the identification of heterozygous carriers as an initial step toward establishing a breeding colony of MPS IIIA dogs for the study of various therapeutic strategies targeted to the central nervous system.
authors.affiliation: Lysosomal Diseases Research Unit, Department of Chemical Pathology, Women's and Children's Hospital, 72 King William Road, North Adelaide, SA, 5006, Australia.
authors.forename: Gouri
authors.initials: G
authors.lastname: Yogalingam
authors.forename: Tony
authors.initials: T
authors.lastname: Pollard
authors.forename: Briony
authors.initials: B
authors.lastname: Gliddon
authors.forename: Robert D
authors.initials: RD
authors.lastname: Jolly
authors.forename: John J
authors.initials: JJ
authors.lastname: Hopwood
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000201:enzymology / Q000235:genetics*; D004285:Dogs; D005787:Gene Frequency; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009084:Mucopolysaccharidosis III / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D016254:Mutagenesis, Insertional; D009520:New Zealand; D012689:Sequence Homology, Nucleic Acid
chemical_list: D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase