OMIA 000666-9615 : Mucopolysaccharidosis VI in Canis lupus familiaris

In other species: domestic cat

Possibly relevant human trait(s) and/or gene(s) (MIM number): 253200

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2004

Cross-species summary: This disorder is a lysosomal storage disease, caused by a deficiency of the lysosomal enzyme N-acetylgalactosamine 4-sulfatase.

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous disorder in other species), Berman et al. (2004) were the first to report a molecular basis of this disorder, as follows: "When the DNA coding sequence from miniature pinschers affected with MPS VI was compared to the normal canine sequence, a single missense mutation (G to A) was identified. This mutation, occurring in exon V, replaces the tiny amino acid glycine with a bulky arginine in a highly conserved region of the protein and is found only in affected dogs."

Jolly et al. (2012) reported a different mutation in a Miniature Poodle-type of dog: "A novel homozygous 22 base pair (bp) deletion in exon 1 of this enzyme's [ARSB] gene was identified (c.103_124del), which caused a frameshift and subsequent premature stop codon."

Pérez et al. (2015) reported an affected Miniature Schnauzer homozygous for the same variant as reported by Berman et al. (2004).

Wang et al. (2017) reported an affected Great Dane homozygous for a "nonsense mutation (c.295C>T) in exon 1, replacing glutamine with a premature stop codon (p.Gln99*), predicting no enzyme synthesis".

Breeds: Chesapeake Bay Retriever, Great Dane, Miniature Pinscher, Miniature Poodle, Miniature Schnauzer, Toy Poodle, Welsh Corgi.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ARSB arylsulfatase B Canis lupus familiaris 3 NC_006585.3 (27870111..28034906) ARSB 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
Miniature Pinscher Miniature Schnauzer Mucopolysaccharidosis VI ARSB missense c.??G>A p.G??R 2004 Reference not in PubMed; see OMIA 000666-9615 for reference details
Miniature Poodle Mucopolysaccharidosis VI ARSB deletion, gross (>20) CanFam3.1 3 g.27870253_27870274del c.103_124del p.Ala35GlyfsTer108 2012 22329490 Variant information kindly provided by Karthik Raj and Urs Giger
Great Dane Mucopolysaccharidosis VI ARSB nonsense (stop-gain) CanFam3.1 3 g.27870445C>T c.295C>T p.Q99* 2017 29157190 Variant information kindly provided by Karthik Raj and Urs Giger, and confirmed by Ensembl's VEP

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.
2017 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 :300985817732115, 2017. Pubmed reference: 29157190. DOI: 10.1177/0300985817732115.
2015 Pérez, M.L., Kridel, H.A., Gallagher, A., Sheppard, B.J., Reese, S., Kondo, H., Alleman, R., Giger, U. :
Mucopolysaccharidosis type VI in a juvenile miniature schnauzer dog with concurrent hypertriglyceridemia, necrotizing pancreatitis, and diabetic ketoacidosis. Can Vet J 56:272-7, 2015. Pubmed reference: 25750448.
2012 Jolly, R.D., Hopwood, J.J., Marshall, N.R., Jenkins, K.S., Thompson, D.J., Dittmer, K.E., Thompson, J.C., Fedele, A.O., Raj, K., Giger, U. :
Mucopolysaccharidosis type VI in a Miniature Poodle-type dog caused by a deletion in the arylsulphatase B gene. N Z Vet J 60:183-8, 2012. Pubmed reference: 22329490. DOI: 10.1080/00480169.2011.642791.
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.
2004 Berman, L., Foureman, P., Steiger, K. et al. :
Mucopolysaccharidosis type VI caused by a point mutation in the miniature Pinscher and a deletion in the miniature Schnauzer [abstract] 2nd International Conference on Advances in Canine & Feline Genomics. Utrecht, The Netherlands :60, 2004.
Foureman, P., Berman, L., Stieger, K., Van Hoeven, M., Ellinwood, N. M., Haskins, M. E., Kirkness, E., Giger, U. :
Mucopolysaccharidosis type VI in miniature pinschers: Screening for the mutation Journal of Veterinary Internal Medicine 18:408-409 (abstract), 2004.
1995 Neer, TM., Dial, SM., Pechman, R., Wang, P., Oliver, JL., Giger, U. :
Clinical vignette. Mucopolysaccharidosis VI in a miniature pinscher. J Vet Intern Med 9:429-33, 1995. Pubmed reference: 8558492.

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