OMIA:001342-9615 : Mucopolysaccharidosis IIIB in Canis lupus familiaris (dog)

In other species: emu , pig , taurine cattle

Categories: Lysosomal storage disease

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 252920 (trait) , 609701 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: Also known as Sanfilippo syndrome type B

Molecular basis: Raj et al. (2020) sequenced "All six exons and adjacent regions of the [comparative candidate] NAGLU gene . . . from six healthy appearing and three affected Schipperkes" and discovered a likely causal variant, namely "an insertion consisting of a 40–70 bp poly-A and an 11 bp duplication of the exonic region preceding the poly-A (XM_548088.6:c.2110_2111ins[A(40_70);2100_2110]) is predicted to insert a stretch of 13 or more lysines followed by either an in-frame insertion of a repeat of the four amino acids preceding the lysines, or a frameshift. The clinically affected Schipperkes were homozygous for this insertion, and the sequenced healthy dogs were either heterozygous or homozygous for the wild-type allele".

Clinical features: Affected dogs show clinical signs of cerebellar disease including ataxia and tremor with adult onset at approximately three years of age (Ellinwood et al., 2003).

Pathology: Egeland et al. (2020) "evaluated the naturally occurring canine model of MPS IIIB for the onset and progression of biochemical and neuropathological changes during the preclinical stages (onset approximately 24–30 months of age) of canine MPS IIIB disease. Even by 1 month of age, MPS IIIB dogs had elevated HS levels in brain and cerebrospinal fluid. Analysis of histopathology of several disease-relevant regions of the forebrain demonstrated progressive lysosomal storage and microglial activation despite a lack of cerebrocortical atrophy in the oldest animals studied. More pronounced histopathology changes were detected in the cerebellum, where progressive lysosomal storage, astrocytosis and microglial activation were observed. Microglial activation was particularly prominent in cerebellar white matter and within the deep cerebellar nuclei, where neuron loss also occurred."

Prevalence: Raj et al. (2020) reported that "Screening of Schipperkes from North America, Europe, Australasia, and Russia revealed carrier dogs in all these regions, indicating the worldwide distribution of the mutant allele".

Control: Raj et al. (2020): "From 2003–2019, 3219 Schipperkes were genotyped. Of these, 1.5% were homozygous for this insertion and found to be clinically affected, and 23.6% were heterozygous for the insertion and were clinically healthy, the remaining 74.9% were homozygous for the wild-type and were also clinically healthy. The number of dogs homozygous and heterozygous for the insertion declined rapidly after the initial years of genotyping, documenting the benefit of a DNA screening program in a breed with a small gene pool."

Genetic testing: The results of 17 years of testing for this variant are reported under the "Control" heading above and presented in detail in Table 2 and Figure 3 of Raj et al. (2020).

Breed: Schipperke (Dog) (VBO_0201184).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NAGLU N-acetylglucosaminidase, alpha Canis lupus familiaris 9 NC_051813.1 (21133008..21126245) NAGLU Homologene, Ensembl , NCBI gene


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 Year Published PubMed ID(s) Acknowledgements
956 Schipperke (Dog) Mucopolysaccharidosis IIIB NAGLU insertion, gross (>20) Naturally occurring variant CanFam3.1 9 g.20407670_20407671ins[A[(40_70)];20407660_20407670] c.2110_2111ins[A[(40_70)];2100_2110] XM_548088; an insertion of 40 to 70 A nucleotides and an 11bp duplication of the sequence directly upstream of the poly-A 2020 32081995

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2020). OMIA:001342-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2022 Ellinwood, N.M., Valentine, B.N., Hess, A.S., Jens, J.K., Snella, E.M., Jamil, M., Hostetter, S.J., Jeffery, N.D., Smith, J.D., Millman, S.T., Parsons, R.L., Butt, M.T., Chandra, S., Egeland, M.T., Assis, A.B., Nelvagal, H.R., Cooper, J.D., Nestrasil, I., Mueller, B.A., Labounek, R., Paulson, A., Prill, H., Liu, X.Y., Zhou, H., Lawrence, R., Crawford, B.E., Grover, A., Cherala, G., Melton, A.C., Cherukuri, A., Vuillemenot, B.R., Wait, J.C.M., O'Neill, C.A., Pinkstaff, J., Kovalchin, J., Zanelli, E., McCullagh, E. :
Tralesinidase Alfa Enzyme Replacement Therapy Prevents Disease Manifestations in a Canine Model of Mucopolysaccharidosis Type IIIB. J Pharmacol Exp Ther 382:277-286, 2022. Pubmed reference: 35717448. DOI: 10.1124/jpet.122.001119.
2020 Egeland, M.T., Tarczyluk-Wells, M.M., Asmar, M.M., Adintori, E.G., Lawrence, R., Snella, E.M., Jens, J.K., Crawford, B.E., Wait, J.C.M., McCullagh, E., Pinkstaff, J., Cooper, J.D., Ellinwood, N.M. :
Central nervous system pathology in preclinical MPS IIIB dogs reveals progressive changes in clinically relevant brain regions. Sci Rep 10:20365, 2020. Pubmed reference: 33230178. DOI: 10.1038/s41598-020-77032-y.
Raj, K., Ellinwood, N.M., Giger, U. :
An exonic insertion in the NAGLU gene causing Mucopolysaccharidosis IIIB in Schipperke dogs. Sci Rep 10:3170, 2020. Pubmed reference: 32081995. DOI: 10.1038/s41598-020-60121-3.
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.
Switonski, M. :
Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies. J Appl Genet 61:179-186, 2020. Pubmed reference: 32189222. DOI: 10.1007/s13353-020-00554-8.
2011 Ellinwood, N.M., Ausseil, J., Desmaris, N., Bigou, S., Liu, S., Jens, J.K., Snella, E.M., Mohammed, E.E., Thomson, C.B., Raoul, S., Joussemet, B., Roux, F., Chérel, Y., Lajat, Y., Piraud, M., Benchaouir, R., Hermening, S., Petry, H., Froissart, R., Tardieu, M., Ciron, C., Moullier, P., Parkes, J., Kline, K.L., Maire, I., Vanier, M.T., Heard, J.M., Colle, M.A. :
Safe, efficient, and reproducible gene therapy of the brain in the dog models of Sanfilippo and Hurler syndromes. Mol Ther 19:251-9, 2011. Pubmed reference: 21139569. DOI: 10.1038/mt.2010.265.
2003 Ellinwood, N.M., Henthorn, P.S., Giger, U., Haskins, M.E. :
Mucopolysaccharidosis type IIIB: Identification of the causative mutation in the canine model. American Society of Human Genetics Conference :Abstract 1635, 2003.
Ellinwood, NM., Wang, P., Skeen, T., Sharp, NJ., Cesta, M., Decker, S., Edwards, NJ., Bublot, I., Thompson, JN., Bush, W., Hardam, E., Haskins, ME., Giger, U. :
A model of mucopolysaccharidosis IIIB (Sanfilippo syndrome type IIIB): N-acetyl-alpha-D-glucosaminidase deficiency in Schipperke dogs. J Inherit Metab Dis 26:489-504, 2003. Pubmed reference: 14518829.

Edit History

  • Created by Frank Nicholas on 18 Nov 2009
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 21 Sep 2012
  • Changed by Frank Nicholas on 26 Sep 2017
  • Changed by Frank Nicholas on 23 Jan 2018
  • Changed by Frank Nicholas on 24 Feb 2020
  • Changed by Imke Tammen2 on 11 Dec 2020