Mucopolysaccharidosis VI, MPSVI

 

Gene: ARSB

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations: 

Miniature Poodle mutation: Deletion, ARSB gene; c.103_104 del 22pb, p.(A35G fs STOP 108), exon1

Great Dane mutation: Substitution, ARSB gene; c.295 C>T, p.(Q99 STOP)

Miniature Schnauzer mutation: Deletion, ARSB gene; c.-24_32 del

Miniature Pinscher mutation: Substitution, ARSB gene; c.910 G>A, p.(G304R)

Medical system: Metabolic, lysosomal storage disease

Breed: Great Dane, Miniature Pinscher, Poodle - Miniature (Dwarf), Schnauzer - Miniature

Age of onset of symptoms: Young adult

Mucopolysaccharidosis VI is a lysosomal storage disease affecting several dog breeds. There is a deficiency of the enzyme arylsulfatase B which normally breaks down glucosaminoglycans (GAGs), which are large structural sugar molecules found in connective tissue. In the absence of enzyme activity, GAGs accumulate within the lysosomes of cells, resulting in clinical symptoms including skeletal anomalies, joint laxity, growth retardation, tremors, balance problems and opaque corneas. The disease is progressive and the quality of life of the affected animal deteriorates, eventually resulting in euthanasia for humanitarian reasons.

 

References:

OMIA link: [0666-9615]

Raj K, Berman-Booty L, Foureman P, Giger U. (2020) ARSB gene variants causing Mucopolysaccharidosis VI in Miniature Pinscher and Miniature Schnauzer dogs. Anim Genet 51(6) :982-986.  [pubmed/32985704]

Story BD, Miller ME, Bradbury AM, et al. (2020) Canine models of inherited musculoskeletal and neurodegenerative diseases. Front Vet Sci 7:80. [pubmed/32219101]

Wang P, Margolis C, Lin G, et al. (2018) Mucopolysaccharidosis Type VI in a Great Dane Caused by a Nonsense Mutation in the ARSB Gene. Vet Pathol 55:286-293. [pubmed/29157190]

Jolly RD, Hopwood JK, Marshall NR et al. (2012) Mucopolysaccharidosis type VI in a Miniature Poodle-type dog caused by a deletion in the arylsulphataseB gene. New Zealand Veterinary Journal 60(3):183-188. [pubmed/22329490]