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Mucopolysaccharidosis Type VII (GUSB gene, German Shepherd )

Mucopolysaccharidosis Type VII (GUSB gene, German Shepherd )

Mucopolysaccharidosis VII is a lysosomal storage disease caused by mutations in the GUSB gene encoding beta-glucuronidase responsible for the degradation of mucopolysaccharides (glycosaminoglycans) in the lysosome.

Symptoms

Mucopolysaccharidosis VII in dogs is characterized by a number of symptoms. In the first month of life, affected dogs present with facial abnormalities, low-set ears and broad thorax. Corneal opacity becomes evident at 8 weeks, and they also have disproportionately large heads. Excess mucopolysaccharides are detected in the urine. Between the second and fifth month, dogs experience difficulty in standing, joint problems and significant epiphyseal dysplasia. They may also experience cardiac abnormalities, such as mitral insufficiency and aortic aneurysm.

Disease Management

At present, no definitive cure has been found for mucopolysaccharidosis VII. Management of the disease focuses on supportive care and symptomatic treatment to control pain. However, cases have been reported in which gene therapy, using a retroviral vector expressing canine beta-glucuronidase, has been shown to be effective in improving disease symptoms. Genetic testing and breeding strategies are recommended to avoid inheritance of the disease in future generations.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Mucopolysaccharidosis VII is characterized by the accumulation of glycosaminoglycans in lysosomes due to deficiency of beta-glucuronidase encoded by the GUSB gene. Beta-glucuronidase is an acid hydrolase that breaks down glucuronate-containing glycosaminoglycans. Lack or dysfunction of this enzyme results in the accumulation of glycosaminoglycans in lysosomes, leading to the characteristic symptoms of the disease. A study by Ray et al. (1998) identified a likely causative mutation (c.497G>A) for mucopolysaccharidosis VII in the German Shepherd breed. This mutation causes a change from arginine to histidine in the beta-glucuronidase protein, resulting in a significant decrease in its enzymatic activity, especially in affected dogs. Carrier dogs retain between 40% and 60% of the enzymatic activity of beta-glucuronidase.

Most affected breeds

German Shepherd Dog

Bibliography

Ray J, Bouvet A, DeSanto C,et al. Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine MPS VII, and retroviral vector-mediated correction of MPS VII cells. Genomics. 1998 Mar 1;48(2):248-53.

Ray J, Scarpino V, Laing C,et al. Biochemical basis of the beta-glucuronidase gene defect causing canine mucopolysaccharidosis VII. J Hered. 1999 Jan-Feb;90(1):119-23.