OMIA 000664-9615 : Mucopolysaccharidosis I in Canis lupus familiaris

In other species: domestic cat , cattle

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 607014 , 607015 , 607016

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1992

Cross-species summary: Also known as Hurler syndrome

Species-specific name: Mucopolysaccharidosis I

Species-specific symbol: MPS I

Species-specific description: The mucopolysaccharidoses (MPS) are a group of hereditary diseases characterized by defective metabolism of glycosaminoglycans (mucopolysaccharides), which accumulate in lysosomes in various tissues.

History: In 1982 a family of Plott Hounds was recognized, in which three littermates were affected by MPS I. The clinical symptoms comprised growth retardation, joint problems, progressive lameness and visual impairment, caused by corneal clouding. Shull et al. provided a detailed pathological description (Shull et al. 1982). One of the affected dogs was used to establish a research colony, which was used over many years to evaluate treatment options for human MPS I.

Mapping: Due to unknown reasons the IDUA gene is currently not annotated in NCBI's CanFam 3.1 genome assembly. However, this curator (T.L.) thinks that the canine IDUA gene exists and is highly conserved with respect to other mammalian IDUA orthologs. There is possibly a problem with NCBI's automated annotation pipeline of the dog genome as the IDUA gene is overlapping with the SLC26A1 gene, which is transcribed from the opposite DNA strand.

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the same disorder in humans), Menon et al. (1992) showed the molecular basis for this disorder in Plott Hounds to be a "G>A transition in the donor splice site of intron 1" of the IDUA gene which encodes alpha-L-iduronidase. As explained by Menon et al. (1992), "The mutation causes retention of intron 1 in the RNA and creates a premature termination codon at the exon-intron junction." According to current nomenclature, the variant would be c.155+1G>A.

Breed: Plott Hound.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
IDUA iduronidase, alpha-L- Canis lupus familiaris - no genomic information (-..-) IDUA Ensembl

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
Plott Hound Mucopolysaccharidosis I IDUA splicing CanFam3.1 3 g.91534420G>A c.155+1G>A 1992 1339393 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.
2017 Middleton, D.M., Li, J.Y., Chen, S.D., White, L.E., Dickson, P., Ellinwood, N.M., Provenzale, J.M. :
Diffusion tensor imaging findings suggestive of white matter alterations in a canine model of mucopolysaccharidosis type I. Neuroradiol J :1971400917715792, 2017. Pubmed reference: 28695759. DOI: 10.1177/1971400917715792.
2016 Hinderer, C., Bell, P., Louboutin, J.P., Katz, N., Zhu, Y., Lin, G., Choa, R., Bagel, J., O'Donnell, P., Fitzgerald, C.A., Langan, T., Wang, P., Casal, M.L., Haskins, M.E., Wilson, J.M. :
Neonatal tolerance induction enables accurate evaluation of gene therapy for MPS I in a canine model. Mol Genet Metab 119:124-30, 2016. Pubmed reference: 27386755. DOI: 10.1016/j.ymgme.2016.06.006.
Khalid, O., Vera, M.U., Gordts, P.L., Ellinwood, N.M., Schwartz, P.H., Dickson, P.I., Esko, J.D., Wang, R.Y. :
Immune-Mediated Inflammation May Contribute to the Pathogenesis of Cardiovascular Disease in Mucopolysaccharidosis Type I. PLoS One 11:e0150850, 2016. Pubmed reference: 26986213. DOI: 10.1371/journal.pone.0150850.
Simonaro, C.M., Tomatsu, S., Sikora, T., Kubaski, F., Frohbergh, M., Guevara, J.M., Wang, R.Y., Vera, M., Kang, J.L., Smith, L.J., Schuchman, E.H., Haskins, M.E. :
Pentosan Polysulfate: Oral Versus Subcutaneous Injection in Mucopolysaccharidosis Type I Dogs. PLoS One 11:e0153136, 2016. Pubmed reference: 27064989. DOI: 10.1371/journal.pone.0153136.
2015 Choi, J., Dickson, P., Calabrese, E., Chen, S., White, L., Ellingwood, M., Provenzale, J.M. :
Predicting degree of myelination based on diffusion tensor imagining of canines with mucopolysaccharidosis type I. Neuroradiol J 28:562-73, 2015. Pubmed reference: 26475483. DOI: 10.1177/1971400915609351.
Hinderer, C., Bell, P., Louboutin, J.P., Zhu, Y., Yu, H., Lin, G., Choa, R., Gurda, B.L., Bagel, J., O'Donnell, P., Sikora, T., Ruane, T., Wang, P., Tarantal, A.F., Casal, M.L., Haskins, M.E., Wilson, J.M. :
Neonatal Systemic AAV Induces Tolerance to CNS Gene Therapy in MPS I Dogs and Nonhuman Primates. Mol Ther 23:1298-307, 2015. Pubmed reference: 26022732. DOI: 10.1038/mt.2015.99.
Provenzale, J.M., Nestrasil, I., Chen, S., Kan, S.H., Le, S.Q., Jens, J.K., Snella, E.M., Vondrak, K.N., Yee, J.K., Vite, C.H., Elashoff, D., Duan, L., Wang, R.Y., Ellinwood, N.M., Guzman, M.A., Shapiro, E.G., Dickson, P.I. :
Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I. Exp Neurol 273:1-10, 2015. Pubmed reference: 26222335. DOI: 10.1016/j.expneurol.2015.07.021.
2013 Chiaro, J.A., Baron, M.D., Del Alcazar, C.M., O'Donnell, P., Shore, E.M., Elliott, D.M., Ponder, K.P., Haskins, M.E., Smith, L.J. :
Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs. Bone 55:78-83, 2013. Pubmed reference: 23563357. DOI: 10.1016/j.bone.2013.03.014.
Vite, C.H., Nestrasil, I., Mlikotic, A., Jens, J.K., Snella, E.M., Gross, W., Shapiro, E.G., Kovac, V., Provenzale, J.M., Chen, S., Le, S.Q., Kan, S.H., Banakar, S., Wang, R.Y., Haskins, M.E., Ellinwood, N.M., Dickson, P.I. :
Features of brain MRI in dogs with treated and untreated mucopolysaccharidosis type I. Comp Med 63:163-73, 2013. Pubmed reference: 23582423.
2011 Chen, A., Vogler, C., Mcentee, M., Hanson, S., Matthew Ellinwood, N., Jens, J., Snella, E., Passage, M., Le, S., Guerra, C., Dickson, P. :
Glycosaminoglycan storage in neuroanatomical regions of mucopolysaccharidosis I dogs following intrathecal recombinant human iduronidase. APMIS 119:513-521, 2011. Pubmed reference: 21749451. DOI: 10.1111/j.1600-0463.2011.02760.x.
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.
Lyons, JA., Dickson, PI., Wall, JS., Passage, MB., Ellinwood, NM., Kakkis, ED., McEntee, MF. :
Arterial pathology in canine mucopolysaccharidosis-I and response to therapy. Lab Invest 91:665-74, 2011. Pubmed reference: 21383673. DOI: 10.1038/labinvest.2011.7.
Newkirk, KM., Atkins, RM., Dickson, PI., Rohrbach, BW., McEntee, MF. :
Ocular lesions in canine mucopolysaccharidosis I and response to enzyme replacement therapy. Invest Ophthalmol Vis Sci 52:5130-5, 2011. Pubmed reference: 21436264. DOI: 10.1167/iovs.10-6751.
2010 Dickson, PI., Hanson, S., McEntee, MF., Vite, CH., Vogler, CA., Mlikotic, A., Chen, AH., Ponder, KP., Haskins, ME., Tippin, BL., Le, SQ., Passage, MB., Guerra, C., Dierenfeld, A., Jens, J., Snella, E., Kan, SH., Ellinwood, NM. :
Early versus late treatment of spinal cord compression with long-term intrathecal enzyme replacement therapy in canine mucopolysaccharidosis type I. Mol Genet Metab 101:115-22, 2010. Pubmed reference: 20655780. DOI: 10.1016/j.ymgme.2010.06.020.
Dierenfeld, AD., McEntee, MF., Vogler, CA., Vite, CH., Chen, AH., Passage, M., Le, S., Shah, S., Jens, JK., Snella, EM., Kline, KL., Parkes, JD., Ware, WA., Moran, LE., Fales-Williams, AJ., Wengert, JA., Whitley, RD., Betts, DM., Boal, AM., Riedesel, EA., Gross, W., Ellinwood, NM., Dickson, PI. :
Replacing the enzyme alpha-L-iduronidase at birth ameliorates symptoms in the brain and periphery of dogs with mucopolysaccharidosis type I. Sci Transl Med 2:60ra89, 2010. Pubmed reference: 21123810. DOI: 10.1126/scitranslmed.3001380.
Hordeaux, J., Deniaud, J., Bemelmans, I., Bertrand, L., Moreau, S., Amiaud, J., Wyers, M., Cherel, Y., Colle, MA. :
Histopathologic Changes of the Ear in Canine Models of Mucopolysaccharidosis Types I and VII. Vet Pathol :, 2010. Pubmed reference: 20930106. DOI: 10.1177/0300985810384413.
Metcalf, JA., Linders, B., Wu, S., Bigg, P., O'Donnell, P., Sleeper, MM., Whyte, MP., Haskins, M., Ponder, KP. :
Upregulation of elastase activity in aorta in mucopolysaccharidosis I and VII dogs may be due to increased cytokine expression. Mol Genet Metab 99:396-407, 2010. Pubmed reference: 20044292. DOI: 10.1016/j.ymgme.2009.12.003.
2009 Carlstrom, LP., Jens, JK., Dobyns, ME., Passage, M., Dickson, PI., Ellinwood, NM. :
Inadvertent propagation of factor VII deficiency in a canine mucopolysaccharidosis type I research breeding colony. Comp Med 59:378-82, 2009. Pubmed reference: 19712579.
Passage, MB., Krieger, AW., Peinovich, MC., Lester, T., Le, SQ., Dickson, PI., Kakkis, ED. :
Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs. J Inherit Metab Dis :, 2009. Pubmed reference: 19562502. DOI: 10.1007/s10545-009-1198-5.
2008 Dickson, P., Peinovich, M., Mcentee, M., Lester, T., Le, S., Krieger, A., Manuel, H., Jabagat, C., Passage, M., Kakkis, ED. :
Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I. J Clin Invest 118:2868-76, 2008. Pubmed reference: 18654672. DOI: 10.1172/JCI36521.
Herati, RS., Knox, VW., O'Donnell, P., D'Angelo, M., Haskins, ME., Ponder, KP. :
Radiographic evaluation of bones and joints in mucopolysaccharidosis I and VII dogs after neonatal gene therapy. Mol Genet Metab 95:142-51, 2008. Pubmed reference: 18707908. DOI: 10.1016/j.ymgme.2008.07.003.
2007 Traas, AM., Wang, P., Ma, X., Tittiger, M., Schaller, L., O'Donnell, P., Sleeper, MM., Vite, C., Herati, R., Aguirre, GD., Haskins, M., Ponder, KP. :
Correction of clinical manifestations of canine mucopolysaccharidosis I with neonatal retroviral vector gene therapy. Mol Ther 15:1423-31, 2007. Pubmed reference: 17519893. DOI: 10.1038/sj.mt.6300201.
2004 Kakkis, E., Mcentee, M., Vogler, C., Le, S., Levy, B., Belichenko, P., Mobley, W., Dickson, P., Hanson, S., Passage, M. :
Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I. Mol Genet Metab 83:163-74, 2004. Pubmed reference: 15464431. DOI: 10.1016/j.ymgme.2004.07.003.
2002 Meertens, L., Zhao, Y.J., Rosic-Kablar, S., Li, L.H., Chan, K., Dobson, H., Gartley, C., Lutzko, C., Hopwood, J., Kohn, D., Kruth, S., Hough, M.R., Dube, I.D. :
In utero injection of alpha-L-iduronidase-carrying retrovirus in canine mucopolysaccharidosis type I: Infection of multiple tissues and neonatal gene expression Human Gene Therapy 13:1809-1820, 2002. Pubmed reference: 12396614. DOI: 10.1089/104303402760372918.
1999 Lutzko, C., Kruth, S., Abrams-Ogg, A.C.G., Lau, K., Li, L.H., Clark, B.R., Ruedy, C., Nanji, S., Foster, R., Kohn, D., Shull, R., Dube, I.D. :
Genetically corrected autologous stem cells engraft, but host immune responses limit their utility in canine alpha-L-iduronidase deficiency Blood 93:1895-1905, 1999. Pubmed reference: 10068662.
Lutzko, C., Omori, F., Abrams-Ogg, A.C.G., Shull, R., Li, L.H., Lau, K., Ruedy, C., Nanji, S., Gartley, C., Dobson, H., Foster, R., Kruth, S., Dube, I.D. :
Gene therapy for canine alpha-L-iduronidase deficiency: In utero adoptive transfer of genetically corrected hematopoietic progenitors results in engraftment but not amelioration of disease Human Gene Therapy 10:1521-1532, 1999. Pubmed reference: 10395377. DOI: 10.1089/10430349950017851.
1998 Mcentee, M.F., Wright, K.N., Wanless, I., Denovo, R., Schneider, J.F., Shull, R. :
Noncirrhotic portal hypertension and nodular regenerative hyperplasia of the liver in dogs with mucopolysaccharidosis type I Hepatology 28:385-390, 1998. Pubmed reference: 9696001. DOI: 10.1002/hep.510280214.
1996 Kakkis, E.D., Mcentee, M.F., Schmidtchen, A., Neufeld, E.F., Ward, D.A., Gompf, R.E., Kania, S., Bedolla, C., Chien, S.L., Shull, R.M. :
Long-term and high-dose trials of enzyme replacement therapy in the canine model of mucopolysaccharidosis Biochemical & Molecular Medicine 58:156-167, 1996.
Kruth, S. :
Canine models for gene therapy Transfusion Science 17:71-77, 1996.
Shull, R.M., Lu, X.C., Mcentee, M.F., Bright, R.M., Pepper, K.A., Kohn, D.B. :
Myoblast gene therapy in canine mucopolysaccharidosis i - abrogation by an immune response to alpha-l-iduronidase Human Gene Therapy 7:1595-1603, 1996. Pubmed reference: 8864760. DOI: 10.1089/hum.1996.7.13-1595.
Shull, R., Lu, X.C., Dube, I., Lutzko, C., Kruth, S., Abramsogg, A., Kiem, H.P., Goehle, S., Schuening, F., Millan, C., Carter, R. :
Humoral immune response limits gene therapy in canine MPS I Blood 88:377-379, 1996. Pubmed reference: 8704199.
1994 Shull, R.M., Kakkis, E.D., Mcentee, M.F., Kania, S.A., Jonas, A.J., Neufeld, E.F. :
Enzyme replacement in a canine model of Hurler syndrome Proceedings of the National Academy of Sciences of the United States of America 91:12937-12941, 1994. Pubmed reference: 7809150.
1992 Menon, K.P., Tieu, P.T., Neufeld, E.F. :
Architecture of the Canine IDUA Gene and Mutation Underlying Canine Mucopolysaccharidosis-I Genomics 14:763-768, 1992. Pubmed reference: 1339393.
Stoltzfus, L.J., Sosapineda, B., Moskowitz, S.M., Menon, K.P., Dlott, B., Hooper, L., Teplow, D.B., Shull, R.M., Neufeld, E.F. :
Cloning and Characterization of cDNA Encoding Canine alpha-L- Iduronidase - Messenger RNA Deficiency in Mucopolysaccharidosis-I Dog Journal of Biological Chemistry 267:6570-6575, 1992. Pubmed reference: 1551868.
1990 Gompf, R.E., Shull, R.M., Breider, M.A., Scott, J.A., Constantopoulos, G.C. :
Cardiovascular Changes After Bone Marrow Transplantation in Dogs with Mucopolysaccharidosis-I American Journal of Veterinary Research 51:2054-2060, 1990. Pubmed reference: 2150744.
1989 Breider, M.A., Shull, R.M., Constantopoulos, G. :
Long-Term Effects of Bone Marrow Transplantation in Dogs with Mucopolysaccharidosis 1 American Journal of Pathology 134:677-692, 1989. Pubmed reference: 2493739.
Constantopoulos, G., Scott, J.A., Shull, R.M. :
Corneal Opacity in Canine MPS-I - Changes After Bone Marrow Transplantation Investigative Ophthalmology & Visual Science 30:1802-1807, 1989. Pubmed reference: 2503461.
1982 Shull, R.M., Munger, R.J., Spellacy, E., Hall, C.W., Constantopoulos, G., Neufeld, E.F. :
Canine alpha-L-iduronidase deficiency. A model of mucopolysaccharidosis I. Am J Pathol 109:244-8, 1982. Pubmed reference: 6215865.

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  • Created by Frank Nicholas on 18 Nov 2009
  • Changed by Frank Nicholas on 07 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
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  • Changed by Frank Nicholas on 23 Jan 2018