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Mucopolysaccharidosis VII Shepherd Type (MPS VII)
| Acronym: | MPS VII |
| Gene: | GUSB |
| Mutation: | c.497G>A |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Mucopolysaccharidosis VII Shepherd Type (MPS VII) is a hereditary lysosomal storage disorder affecting Shepherd breeds, such as Belgian Shepherd Dog, German Shepherd Dog, and White Swiss Shepherd Dog. It is a part of a bigger group of disorders, mucopolysaccharidoses. Until now, eleven types of mucopolysaccharidosis have been differentiated in humans. They vary in clinical symptoms, but some characteristics are common to all forms, such as dwarfism, undeveloped epiphyseal centers, dysostosis multiplex, facial dysmorphia, corneal clouding, and organomegaly. They are known to affect humans, mice, dogs, and cats. Mucopolysaccharidosis type VII was first time reported in a mixed breed dog in the 1990s. It is also known as the ‘Sly syndrome’. The extracellular matrix (ECM) is the main component of bone and other connective tissues. It consists mainly of collagen and proteoglycans. Several skeletal disorders have been associated with mutations in genes associated with structural proteins of the extracellular matrix.
Skeletal deformities are also characteristic symptoms of lysosomal storage disorders, and mucopolysaccharidoses. These disorders, lysosomal enzymes, acid hydrolase β-glucuronidase, are dysfunctional, which results in the accumulation of glycosaminoglycans (GAG) in lysosomes. GAG accumulation is happening in lysosomes in different cell types, but mainly in the connective tissues. The first symptoms appear between 4 to 8 weeks of age. Affected puppies are unable to walk and function properly. Severe growth retardation is recognized, where affected puppies usually weigh 35% less than their healthy littermates. In the hind legs, weakness is present, which eventually progresses into the dysfunction of all limbs. The Head appears disproportionally large with a short muzzle, broad face, low set ears, and domed skull. Eyes seem cloudy and smaller than of the healthy littermates. No behavioral changes or changes in appetite have been observed in affected puppies. Except for growth retardation, other typical clinical signs are dwarfism, facial and also other skeletal dysmorphisms, such as epiphyseal dysplasia of the vertebra and long bones, and corneal clouding. Joints are extremely loose and easily subluxated. Cardiac abnormalities have been reported as well. Due to poor quality of life, affected dogs are often euthanized. Mucopolysaccharidosis VII Shepherd Type (MPS VII) is caused by a missense mutation of the GUSB gene encoding lysosomal enzyme acid hydrolase β-glucuronidase. The disorder is inherited as an autosomal recessive trait. Healthy parents of an affected dog are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Haskins ME, Aguirre GD, Jezyk PF, Schuchman EH, Desnick RJ, Patterson DF. Mucopolysaccharidosis type VII (Sly Syndrome). Beta-glucuronidase-deficient mucopolysaccharidosis in the dog. Am J Pathol. 1991 Jun;138(6):1553-5.
Ray J, Bouvet A, DeSanto C, Fyfe JC, Xu D, Wolfe JH, Aguirre GD, Patterson DF, Haskins ME, Henthorn PS. 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, Haskins ME, Ray K. Am J Vet Res. Molecular diagnostic tests for ascertainment of genotype at the mucopolysaccharidosis type VII locus in dogs. 1998 Sep; 59(9):1092-5.
Silverstein Dombrowski DC, Carmichael KP, Wang P, O’Malley TM, Haskins ME, Giger U. Mucopolysaccharidosis type VII in a German Shepherd Dog. J Am Vet Med Assoc. 2004 Feb 15;224(4):553-7, 532-3.