OMIA 000666-9615 : Mucopolysaccharidosis VI in Canis lupus familiaris

In other species: domestic cat

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 253200 (trait) , 611542 (gene)

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." This result was finally published in a refereed paper by Raj et al. (2020).

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".

Raj et al. (2020): "A missense variant (NM_001048133.1:c.910G>A) was found in exon 5 of MPS VI‐affected Miniature Pinschers that is predicted to result in a deleterious amino acid substitution of a highly conserved glycine to arginine (NP_001041598.1:p.Gly304Arg). In MPS VI‐affected Miniature Schnauzers, a 56 bp deletion (NM_001048133.1:c.‐24_32del) was found at the junction of exon 1 and its upstream region, predicting no enzyme synthesis. All clinically affected Miniature Pinschers and Miniature Schnauzers were homozygous for the respective variants, and screened healthy dogs in each breed were either heterozygous or homozygous for the wt allele."

Prevalence: Raj et al. (2020): "Over the past 17 years, a total of 425 Miniature Pinschers and two mixed‐breed dogs from the USA, Canada and UK were genotyped; of them 18 (4.2%) were homozygous for the missense variant [c.910G>A], including two mixed‐breed dogs, 78 (18.3%) were heterozygous and 331 (77.5%) were homozygous for the wt allele. All of the genotyped Miniature Pinschers that had clinical signs consistent with MPS VI were homozygous for the missense variant. . . . Whereas the Miniature Pinscher variant seemed to occur commonly (0.133 allele frequency), the Miniature Schnauzer variant was presumed to be rare"

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_051807.1 (27790052..27973468) 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.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
56 Miniature Schnauzer Mucopolysaccharidosis VI ARSB deletion, gross (>20) Naturally occurring variant CanFam3.1 3 g.27870127_27870182del c.-24_32del NM_001048133.1 2020 32985704 g. coordinate kindly provided by Karthik Raj 29 Oct 2020
640 Miniature Poodle Mucopolysaccharidosis VI ARSB deletion, gross (>20) Naturally occurring variant CanFam3.1 3 g.27870253_27870274del c.103_124del p.(A35Gfs*108) NM_001048133.1; NP_001041598.1 2012 22329490 Variant information initially provided by Karthik Raj and Urs Giger
859 Great Dane Mucopolysaccharidosis VI ARSB nonsense (stop-gain) Naturally occurring variant CanFam3.1 3 g.27870445C>T c.295C>T p.(Q99*) NM_001048133.1; NP_001041598.1 2018 29157190 Variant information initially provided by Karthik Raj and Urs Giger, and confirmed by Ensembl's VEP
1258 Miniature Pinscher Mucopolysaccharidosis VI ARSB missense Naturally occurring variant CanFam3.1 3 g.27950471G>A c.910G>A p.(G304R) NM_001048133.1; NP_001041598.1 2020 32985704 g. coordinate kindly provided by Karthik Raj 29 Oct 2020

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.
2020 Raj, K., Berman-Booty, L., Foureman, P., Giger, U. :
ARSB gene variants causing Mucopolysaccharidosis VI in Miniature Pinscher and Miniature Schnauzer dogs. Anim Genet :, 2020. Pubmed reference: 32985704. DOI: 10.1111/age.13005.
Story, B.D., Miller, M.E., Bradbury, A.M., Million, E.D., Duan, D., Taghian, T., Faissler, D., Fernau, D., Beecy, S.J., Gray-Edwards, H.L. :
Canine models of inherited musculoskeletal and neurodegenerative diseases. Front Vet Sci 7:80, 2020. Pubmed reference: 32219101. DOI: 10.3389/fvets.2020.00080.
2018 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 55:286-293, 2018. 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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