Mucopolysaccharidosis VII in Brazilian Terriers

Mucopolysaccharidosis VII is a lysosomal storage disease in which mucopolysaccharides (glycosaminoglycans - dermatan, heparan and chondroitin sulphate) accumulate in lysosomes. The accumulation results from a deficiency of the lysosomal enzyme hydrolase -glucuronidase. Clinical signs include facial dysmorphia (already in puppies at 4 weeks of age, shortening and widening of the muzzle and low-set ears are seen), diffuse corneal opacity, presence of glycosaminoglycans in the urine, bone lesions, lack of body growth relative to the head, later joint problems, and even inability to stand. Various cardiac abnormalities may also occur. Affected dogs have very low -glucuronidase activity, while carriers have 40-60% activity of this enzyme compared to normal healthy dogs.

The cause of the disease in Brazilian terriers is a missense mutation c.866C>T in the gene encoding hydrolase -glucuronidase (GUSB).

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:

Hytönen, M.K., Arumilli, M., Lappalainen, A.K., Kallio, H., Snellman, M., Sainio, K., Lohi, H.: A novel GUSB mutation in Brazilian terriers with severe skeletal abnormalities defines the disease as mucopolysaccharidosis VII. PLoS One 7:e40281, 2012. Pubmed reference: 22815736.