Mucopolysaccharidosis VI in Great Dane

Mucopolysaccharidosis VI is a lysosomal storage disease in which mucopolysaccharides (glycosaminoglycans - dermatan, heparan and chondroitin sulphate) accumulate in lysosomes. The accumulation of mucopolysaccharides results in cellular and organ dysfunction. It results from a deficiency of the lysosomal enzyme N-acetylgalactosamine 4-sulfatase (arylsulfatase B). Clinical signs include growth retardation, facial dysmorphia, skeletal deformities, corneal opacities and amplification of sound phenomena during breathing.

In Great Danes, this disease is caused by the nonsense mutation c.295C>T in the ARSB gene, which encodes the enzyme arylsulfatase B. The mutation leads to the introduction of the premature stop codon and stops the synthesis of the enzyme.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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References:

Wang, P., Margolis, C., Lin, G., Buza, E.L., Quick, S., Raj, K., Han, R., Giger, U. : Mucopolysaccharidosis Type VI in a Great Dane Caused by a Nonsense Mutation in the ARSB Gene. Vet Pathol 55:286-293, 2018. Pubmed reference: 29157190