OMIA 000402-9615 : Gangliosidosis, GM1 in Canis lupus familiaris

See the equivalent entry at NCBI

In other species: domestic cat , cattle , sheep , emu

Possible human homologues (MIM numbers): 230500 , 230650

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key mutation known: yes

Year key mutation first reported: 2000

Cross-species summary: A lysosomal storage disease in which there is a buildup (storage) of GM1 gangliosides (a type of glycolipid) in various tissues, due to the lack of the enzyme beta-galactosidase, whose task is to break down the GM1 ganglioside into its constituents. Characterised by progressive neuromuscular dysfunction and impaired growth from an early age.

Species-specific description: GM1 gangliosidosis is a lysosomal storage disease caused by beta galactosidase deficiency and characterized by progressive neurological deterioration. It is caused by mutations in GLB1, although the mutations differ by breed. There is a genetic test available.

Mapping: CFA23

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Wang et al. (2000) showed that the causative mutation in Portuguese water dogs is a G to A transition in exon 2 of the GLB1 gene, that causes an amino acid change from arginine to histidine in the resultant peptide.

The causative mutation in Shiba dogs is a deletion of a cytosine in exon 15 that causes a premature stop codon in GLB1 (Yamato et al., 2002).

The causative mutation in Alaskan huskies is a 19 base pair duplication in exon 15 that variably disrupts mRNA splicing and result in no functional GLB1 (Kreutzer et al., 2001).

Clinical features: Affected dogs generally have proportional dwarfism, which is easily observed in the Alaskan husky, and all develop progressive cerebellar dysfunction and limb weakness. Signs include weight loss, ataxia, wide-based gait, decreased proprioception, intention tremor of the head, ataxia, hypermetria, dysmetria, internal strabismus, and positional nystagmus. Signs begin around 6 to 8 weeks of age, and are clearly noticeable by 7 months of age. Abnormal endochondral ossification of vertebral epiphyses was visible in radiographs of 5.5 month old affected Alaskan huskies. Affected dogs occasionally have an increase in serum ALP. Coarse facial features are seen in affected English springer spaniels (Müller et al., 2001, Alroy et al., 1992). Bone marrow transplantation therapy was attempted but ineffective in affected Portugese water dogs (O’Brien et al., 1990).

Pathology: Affected dogs are deficient in acid beta-galactosidase and are unable to completely degrade complex oligosaccharides. The result is lysosomal accumulation of GM1 gangliosides and other galactose-containing glycoconjugates with a nonreduced terminal beta-galactosidic linkage (Müller et al., 2001). On histologic examination, most neurons in the central nervous system contain densely packed, PAS positive cytoplasmic inclusions, giving the appearance of foamy or granular cytoplasm. Other changes include mild demyelination, axonal degeneration, significant astrogliosis, and significant loss of oligodendrocytes (Müller et al., 2001). Vacuoles are also found in hepatocytes and renal tubular epithelial cells (Shell et al 1989).

Control: Relatives of affected dogs should be tested and breeding of affected or carrier dogs should be avoided.

Genetic testing: There are tests available to detect the known causative mutations.

Breeds: Alaskan Husky, Beagle, English Springer Spaniel, Portugese water dog, Shiba.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GLB1 galactosidase, beta 1 Canis lupus familiaris 23 NC_006605.3 (3721768..3814209) GLB1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
Shiba Gangliosidosis, GM1 GLB1 deletion, small (<=20) a deletion of a cytosine in exon 15 that causes a premature stop codon in GLB1 2002 12555949
Alaskan Husky Gangliosidosis, GM1 GLB1 insertion, small (<=20) a 19 base pair duplication in exon 15 2001 11355658
Portugese water dog Gangliosidosis, GM1 GLB1 missense c.200G>A p.R60H 2000 11032334

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.
2016 Kohyama, M., Yabuki, A., Ochiai, K., Nakamoto, Y., Uchida, K., Hasegawa, D., Takahashi, K., Kawaguchi, H., Tsuboi, M., Yamato, O. :
In situ detection of GM1 and GM2 gangliosides using immunohistochemical and immunofluorescent techniques for auxiliary diagnosis of canine and feline gangliosidoses. BMC Vet Res 12:67, 2016. Pubmed reference: 27036194. DOI: 10.1186/s12917-016-0691-y.
2013 Broeckx, B.J., Coopman, F., Verhoeven, G.E., Van Haeringen, W., van de Goor, L., Bosmans, T., Gielen, I., Saunders, J.H., Soetaert, S.S., Van Bree, H., Van Neste, C., Van Nieuwerburgh, F., Van Ryssen, B., Verelst, E., Van Steendam, K., Deforce, D. :
The prevalence of nine genetic disorders in a dog population from belgium, the Netherlands and Germany. PLoS One 8:e74811, 2013. Pubmed reference: 24069350. DOI: 10.1371/journal.pone.0074811.
Hasegawa, D., Tamura, S., Nakamoto, Y., Matsuki, N., Takahashi, K., Fujita, M., Uchida, K., Yamato, O. :
Magnetic resonance findings of the corpus callosum in canine and feline lysosomal storage diseases. PLoS One 8:e83455, 2013. Pubmed reference: 24386203. DOI: 10.1371/journal.pone.0083455.
Uddin, M.M., Arata, S., Takeuchi, Y., Chang, H.S., Mizukami, K., Yabuki, A., Rahman, M.M., Kohyama, M., Hossain, M.A., Takayama, K., Yamato, O. :
Molecular epidemiology of canine GM1 gangliosidosis in the Shiba Inu breed in Japan: relationship between regional prevalence and carrier frequency. BMC Vet Res 9:132, 2013. Pubmed reference: 23819787. DOI: 10.1186/1746-6148-9-132.
2012 Hasegawa, D., Yamato, O., Nakamoto, Y., Ozawa, T., Yabuki, A., Itamoto, K., Kuwabara, T., Fujita, M., Takahashi, K., Mizoguchi, S., Orima, H. :
Serial MRI features of canine GM1 gangliosidosis: a possible imaging biomarker for diagnosis and progression of the disease. ScientificWorldJournal 2012:250197, 2012. Pubmed reference: 22536126. DOI: 10.1100/2012/250197.
Rahman, M.M., Kawaguchi, H., Miyoshi, N., Yabuki, A., Nakamoto, Y., Ozawa, T., Yamato, O. :
Pathological features of salivary gland cysts in a Shiba dog with GM1 gangliosidosis: a possible misdiagnosis as malignancy. J Vet Med Sci 74:485-9, 2012. Pubmed reference: 22083095.
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.
2011 Satoh, H., Yamauchi, T., Yamasaki, M., Maede, Y., Yabuki, A., Chang, H.S., Asanuma, T., Yamato, O. :
Rapid detection of GM1 ganglioside in cerebrospinal fluid in dogs with GM1 gangliosidosis using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. J Vet Diagn Invest 23:1202-7, 2011. Pubmed reference: 22362802. DOI: 10.1177/1040638711425592.
2010 Chang, HS., Arai, T., Yabuki, A., Hossain, MA., Rahman, MM., Mizukami, K., Yamato, O. :
Rapid and reliable genotyping technique for GM1 gangliosidosis in Shiba dogs by real-time polymerase chain reaction with TaqMan minor groove binder probes. J Vet Diagn Invest 22:234-7, 2010. Pubmed reference: 20224082.
2009 Kreutzer, R., Kreutzer, M., Sewell, AC., Techangamsuwan, S., Leeb, T., Baumgartner, W. :
Impact of beta-galactosidase mutations on the expression of the canine lysosomal multienzyme complex. Biochim Biophys Acta 1792:982-7, 2009. Pubmed reference: 19607915. DOI: 10.1016/j.bbadis.2009.07.004.
2008 Kreutzer, R., Kreutzer, M., Leeb, T., Baumgartner, W. :
Rapid and accurate G M1-gangliosidosis diagnosis using a parentage testing microsatellite. Mol Cell Probes 22:252-4, 2008. Pubmed reference: 18562164. DOI: 10.1016/j.mcp.2008.05.001.
Nagayasu, A., Nakamura, T., Yamato, O., Tsuzuki, K., Hosaka, Y., Ueda, H., Tangkawattana, P., Takehana, K. :
Morphological analysis of corneal opacity in Shiba dog with GM1 gangliosidosis. J Vet Med Sci 70:881-6, 2008. Pubmed reference: 18840960.
Yamato, O., Jo, EO., Chang, HS., Satoh, H., Shoda, T., Sato, R., Uechi, M., Kawasaki, N., Naito, Y., Yamasaki, M., Maede, Y., Arai, T. :
Molecular screening of canine GM1 gangliosidosis using blood smear specimens after prolonged storage: detection of carriers among shiba dogs in northern Japan. J Vet Diagn Invest 20:68-71, 2008. Pubmed reference: 18182512.
2007 Kreutzer, R., Kreutzer, M., Propsting, MJ., Sewell, AC., Leeb, T., Naim, HY., Baumgartner, W. :
Insights into post-translational processing of beta-galactosidase in an animal model resembling late infantile human G-gangliosidosis. J Cell Mol Med 12:1661-71, 2007. Pubmed reference: 18088383. DOI: 10.1111/j.1582-4934.2007.00204.x.
Satoh, H., Yamato, O., Asano, T., Yonemura, M., Yamauchi, T., Hasegawa, D., Orima, H., Arai, T., Yamasaki, M., Maede, Y. :
Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: possible use for assessment of a therapeutic regimen. Brain Res 1133:200-8, 2007. Pubmed reference: 17196562. DOI: 10.1016/j.brainres.2006.11.039.
2006 Yamato, O., Jo, EO., Satoh, H., Yamauchi, T., Kobayashi, A., Yamasaki, M., Maede, Y. :
Use of amnion and placenta in neonatal screening for canine GM1-gangliosidosis and the risk of diagnostic misclassifications. Vet Clin Pathol 35:91-4, 2006. Pubmed reference: 16511797.
2005 Kreutzer, R., Leeb, T., Muller, G., Moritz, A., Baumgartner, W. :
A duplication in the canine beta-galactosidase gene GLB1 causes exon skipping and GM1-gangliosidosis in Alaskan huskies. Genetics 170:1857-61, 2005. Pubmed reference: 15944348. DOI: 10.1534/genetics.105.042580.
2004 Satoh, H., Yamato, O., Asano, T., Yamasaki, M., Maede, Y. :
Increased concentration of GM1-ganglioside in cerebrospinal fluid in dogs with GM1- and GM2-gangliosidoses and its clinical application for diagnosis. J Vet Diagn Invest 16:223-6, 2004. Pubmed reference: 15152837.
Yamato, O., Jo, EO., Shoda, T., Yamasaki, M., Maede, Y. :
Rapid and simple mutation screening of G(M1) gangliosidosis in Shiba dogs by direct amplification of deoxyribonucleic acid from various forms of canine whole-blood specimens. J Vet Diagn Invest 16:469-72, 2004. Pubmed reference: 15460336.
Yamato, O., Kobayashi, A., Satoh, H., Endoh, D., Shoda, T., Masuoka, Y., Hatakeyama, A., Jo, EO., Asano, T., Yonemura, M., Yamasaki, M., Maede, Y. :
Comparison of polymerase chain reaction-restriction fragment length polymorphism assay and enzyme assay for diagnosis of G(M1)-gangliosidosis in Shiba dogs. J Vet Diagn Invest 16:299-304, 2004. Pubmed reference: 15305740.
2003 Yamato, O., Masuoka, Y., Yonemura, M., Hatakeyama, A., Satoh, H., Kobayashi, A., Nakayama, M., Asano, T., Shoda, T., Yamasaki, M., Ochiai, K., Umemura, T., Maede, Y. :
Clinical and clinico-pathologic characteristics of Shiba dogs with a deficiency of lysosomal acid beta-galactosidase: a canine model of human GM1 gangliosidosis Journal of Veterinary Medical Science 65:213-7, 2003. Pubmed reference: 12655116.
2002 Yamato, O., Endoh, D., Kobayashi, A., Masuoka, Y., Yonemura, M., Hatakeyama, A., Satoh, H., Tajima, M., Yamasaki, M., Maede, Y. :
A novel mutation in the gene for canine acid beta-galactosidase that causes GM1-gangliosidosis in Shiba dogs Journal of Inherited Metabolic Disease 25:525-526, 2002. Pubmed reference: 12555949.
2001 Müller, G., Alldinger, S., Moritz, A., Zurbriggen, A., Kirchhof, N., Sewell, A., Baumgärtner, W. :
GM1-gangliosidosis in Alaskan huskies: clinical and pathologic findings. Vet Pathol 38:281-90, 2001. Pubmed reference: 11355658.
2000 Wang, Z.H., Zeng, B., Shibuya, H., Johnson, G.S., Alroy, J., Pastores, G.M., Raghavan, S., Kolodny, E.H. :
Isolation and characterization of the normal canine beta-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis. J Inherit Metab Dis 23:593-606, 2000. Pubmed reference: 11032334.
Whitfield, P., Johnson, A.W., Dunn, K.A., Delauche, A.J.N., Winchester, B.G., Franklin, R.J.M. :
G(M1)-gangliosidosis in a cross-bred dog confirmed by detection of G(M1)-ganglioside using electrospray ionisation-tandem mass spectrometry Acta Neuropathologica 100:409-414, 2000. Pubmed reference: 10985700.
Yamato, O., Ochiai, K., Masuoka, Y., Hayashida, E., Tajima, M., Omae, S., Iijima, M., Umemura, T., Maede, Y. :
GM1 gangliosidosis in shiba dogs Veterinary Record 146:493-496, 2000. Pubmed reference: 10887996.
1998 Muller, G., Baumgartner, W., Moritz, A., Sewell, A., Kustermannkuhn, B. :
Biochemical findings in a breeding colony of Alaskan huskies suffering from GM(1)-gangliosidosis Journal of Inherited Metabolic Disease 21:430-431, 1998. Pubmed reference: 9700604.
1995 Alroy, J., Knowles, K., Schelling, S.H., Kaye, E.M., Rosenberg, A.E. :
Retarded bone formation in G(M1)-gangliosidosis: A study of the infantile form and comparison with two canine models Virchows Archiv - an International Journal of Pathology 426:141-148, 1995. Pubmed reference: 7757284.
1992 Alroy, J., Orgad, U., Degasperi, R., Richard, R., Warren, C.D., Knowles, K., Thalhammer, J.G., Raghavan, S.S. :
Canine GM1-Gangliosidosis - A Clinical, Morphologic, Histochemical, and Biochemical Comparison of Two Different Models American Journal of Pathology 140:675-689, 1992. Pubmed reference: 1546746.
Fischer, I., Alroy, J. :
Reduced Levels of Neuronal-Specific Microtubule-Associated Protein (MAP2) in Canine G(M1)-Gangliosidosis Neuroscience Research Communications 10:155-161, 1992.
Kaye, E.M., Alroy, J., Raghavan, S.S., Schwarting, G.A., Adelman, L.S., Runge, V., Gelblum, D., Thalhammer, J.G., Zuniga, G. :
Dysmyelinogenesis in Animal Model of GM1 Gangliosidosis Pediatric Neurology 8:255-261, 1992. Pubmed reference: 1388413.
1990 Obrien, J.S., Storb, R., Raff, R.F., Harding, J., Appelbaum, F., Morimoto, S., Kishimoto, Y., Graham, T., Ahernrindell, A., Obrien, S.L. :
Bone Marrow Transplantation in Canine GM1 Gangliosidosis Clinical Genetics 38:274-280, 1990. Pubmed reference: 2125250.
1989 Shell, LG., Potthoff, AI., Carithers, R., Katherman, A., Saunders, GK., Wood, PA., Giger, U. :
Neuronal-visceral GM1 gangliosidosis in Portuguese water dogs. J Vet Intern Med 3:1-7, 1989. Pubmed reference: 2494322.
1988 Saunders, GK., Wood, PA., Myers, RK., Shell, LG., Carithers, R. :
GM1 gangliosidosis in Portuguese water dogs: pathologic and biochemical findings. Vet Pathol 25:265-9, 1988. Pubmed reference: 3136586.
1985 Alroy, J., Orgad, U., Ucci, AA., Schelling, SH., Schunk, KL., Warren, CD., Raghavan, SS., Kolodny, EH. :
Neurovisceral and skeletal GM1-gangliosidosis in dogs with beta-galactosidase deficiency. Science 229:470-2, 1985. Pubmed reference: 3925555.
1982 Rodriguez, M., O'Brien, JS., Garrett, RS., Powell, HC. :
Canine GM1 gangliosidosis. An ultrastructural and biochemical study. J Neuropathol Exp Neurol 41:618-29, 1982. Pubmed reference: 6813429.
Warner, TG., O'Brien, JS. :
Structure analysis of the major oligosaccharides accumulating in canine GM1 gangliosidosis liver. J Biol Chem 257:224-32, 1982. Pubmed reference: 6796586.
1980 Rittmann, LS., Tennant, LL., O'Brien, JS. :
Dog GM1 gangliosidosis: characterization of the residual liver acid beta-galactosidase. Am J Hum Genet 32:880-9, 1980. Pubmed reference: 6778205.
1976 Read, DH., Harrington, DD., Keenana, TW., Hinsman, EJ. :
Neuronal-visceral GM1 gangliosidosis in a dog with beta-galactosidase deficiency. Science 194:442-5, 1976. Pubmed reference: 824730.

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  • Created by Frank Nicholas on 05 Jan 2006
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  • Changed by Frank Nicholas on 12 Dec 2011
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