OMIA 000667-9685 : Mucopolysaccharidosis VII in Felis catus

In other species: dog

Possibly relevant human trait(s) and/or gene(s) (MIM number): 253220

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1999

Cross-species summary: Mucopolysaccharidosis VII is a lysosomal storage disease in which there is a buildup (storage) of mucopolysaccharides (glycosaminoglycans), due to the lack of the lysosomal enzyme acid hydrolase beta-glucuronidase (EC 3.2.1.31).

Species-specific description: This lysosomal storage disease was first described in cats (a black domestic short-haired cat from Switzerland) by Gitzelmann et al. (1994), who reported a lack of the enzyme beta-glucuronidase.

Inheritance: No breeding data available, but presumably autosomal recessive.

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Fyfe et al. (1999) reported the molecular basis of this disorder in cats to be a missense mutation in the GUSB gene encoding the enzyme beta-glucuronidase. The authors reported that this mutation is "a G-to-A transition in the affected cat cDNA that predicted an E351K substitution, destroyed a BssSI site, and eliminated GUSB enzymatic activity in expression studies". According to the variant nomenclature of the year 2013 this corresponds to c.1051G>A or p.E351K.

Wang et al. (2015) reported another causal mutation: "2 unique single base transitions (c.1421T>G and c.1424C>T) in exon 9, altering 2 adjacent codons (p.Ser475Ala and p.Arg476Trp). These amino acid changes are in a highly conserved domain of the GUSB protein and nontolerable to maintain function. Moreover, the p.Arg476Trp mutation previously has been identified in human patients."

Clinical features: (From Gitzelmann et al., 1994) The affected cat was presented at 12-14 weeks of age, with walking difficulties and an enlarged abdomen. He was small for his age, and showed intense licking. He was, however, active and attentive. His face was broad, cheeks were high, and nose was short. There were signs of frontal bossing, corneal clouding, plump front paws with inside rotation, and mild thickening of the skin, especially over the paws. His ears were small and their tips were distorted. Other signs included lengthened tongue, extended abdomen, and funnel-shaped lower thoracic opening. He walked with his weight shifted to his front paws. The clinical course was progressive: the rear legs showed reduced proprioceptivity and no tactile reflexes, hyperreflexia (patellar and tibialis cranialis reflexes), and positive crossed extensor reflexes. Cuticular reflexes were not elicited. Grand mal seizures lasted up to 20 seconds and could be evoked by stimulation of the skin over his back. His neck became stiff, and walking became almost impossible. Excessive scaling of the skin occurred. Patellae could be dislocated with ease; cruciate ligaments were lax. Tongue and first digits became irritated from excessive licking. Growth decelerated. He was euthanased at 5.5-6 months.

Pathology: (From Gitzelmann et al., 1994) Activity of beta-glucuronidase was absent from leucocytes, and was markedly reduced in fibroblasts. Neutrophils were granulated; lymphocytes vacuolated. Positive urine test for sulfated glycosaminoglycans. Foam cells in almost all organs; pancytic storage of floccular material characteristic of mucopolysaccharides. Stored sphingolipids in the form of zebra bodies in ganglion cells of the central nervous system and in smoothh muscle cells of blood vessels.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GUSB glucuronidase, beta Felis catus E3 NC_018738.3 (16116420..16129899) GUSB Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Mucopolysaccharidosis VII GUSB missense c.1421T>G and c.1424C>T p.S475A and p.R476W 2015 26118695
Mucopolysaccharidosis VII GUSB missense Felis_catus_6.2 E3 g.15661641G>A c.1051G>A p.E351K 1999 10366443 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2015 Wang, P., Sorenson, J., Strickland, S., Mingus, C., Haskins, M.E., Giger, U. :
Mucopolysaccharidosis VII in a Cat Caused by 2 Adjacent Missense Mutations in the GUSB Gene. J Vet Intern Med 29:1022-8, 2015. Pubmed reference: 26118695. DOI: 10.1111/jvim.13569.
2012 Sewell, A.C., Haskins, M.E., Giger, U. :
Dried blood spots for the enzymatic diagnosis of lysosomal storage diseases in dogs and cats. Vet Clin Pathol 41:548-57, 2012. Pubmed reference: 23121383. DOI: 10.1111/j.1939-165x.2012.00485.x.
2000 Schultheiss, P.C., Gardner, S.A., Owens, J.M., Wenger, D.A., Thrall, M.A. :
Mucopolysaccharidosis VII in a cat Veterinary Pathology 37:502-505, 2000. Pubmed reference: 11055883.
1999 Fyfe, J.C., Kurzhals, R.L., Lassaline, M.E., Henthorn, P.S., Alur, P.R.K., Wang, P., Wolfe, J.H., Giger, U., Haskins, M.E., Patterson, D.F., Sun, H.C., Jain, S., Yuhki, N. :
Molecular basis of feline beta-glucuronidase deficiency: An animal model of mucopolysaccharidosis VII Genomics 58:121-128, 1999. Pubmed reference: 10366443. DOI: 10.1006/geno.1999.5825.
1994 Gitzelmann, R., Bosshard, N.U., Supertifurga, A., Spycher, M.A., Briner, J., Wiesmann, U., Lutz, H., Litschi, B. :
Feline mucopolysaccharidosis VII due to beta-glucuronidase deficiency Veterinary Pathology 31:435-443, 1994. Pubmed reference: 7941232.

Edit History


  • Created by Frank Nicholas on 10 Sep 2005
  • Changed by Frank Nicholas on 03 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
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