OMIA 001505-9615 : Neuronal ceroid lipofuscinosis, 10 in Canis lupus familiaris
Clinical features: Onset of signs is usually before 2 years of age and includes hypermetria, dysmetria, paraparesis, ataxia, and progressive psychomotor degeneration. Signs progress slowly, with death by 7 years of age (Awano et al., 2006).Unlike many other NCLs, American bulldogs with NCL10 do not show signs of cerebral dysfunction or blindness (Evans et al, 2005). Pathology: Cytoplasmic autofluorescent storage material is present in neurons of the cerebrum, cerebellum, and retina. The most concentrated areas of neuronal cytoplasmic inclusion material is in the gracilic, medial, and lateral cuneate nuclei. Axonal spheroids indicative of neuroaxonal dystrophy are present in the thalamus, caudal medulla, and spinal cord grey matter. Muscle and nerve biopsies have changes consistent with mild denervation (Evans et al., 2005). In the retina, inclusions appear in photoreceptor cells, mostly in cones, in the outer limiting membrane next to the outermost layer of photoreceptor nuclei (Awano et al., 2006).
Prevalence: Allelic frequency was 28% in the American bulldog population studied to identify the causative mutation (Awano et al., 2006). Control: Relatives of affected dogs should be tested. Avoid breeding affected or carrier dogs.
Genetic testing: A genetic test is available. Breed: American Bulldog. Associated gene:
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|CTSD||cathepsin D||Canis lupus familiaris||18||NC_051822.1 (46700871..46691854)||CTSD||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.
|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|
|American Bulldog||Neuronal ceroid lipofuscinosis, 10||CTSD||missense||CanFam3.1||18||g.46013354G>A||c.597G>A||p.M199I||2006||16386934||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
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||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.|
|2017||Katz, M.L., Rustad, E., Robinson, G.O., Whiting, R.E.H., Student, J.T., Coates, J.R., Narfstrom, K. :|
|Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions. Neurobiol Dis :, 2017. Pubmed reference: 28860089. DOI: 10.1016/j.nbd.2017.08.017.|
|2013||Bond, M., Holthaus, S.M., Tammen, I., Tear, G., Russell, C. :|
|Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1832:1842-65, 2013. Pubmed reference: 23338040. DOI: 10.1016/j.bbadis.2013.01.009.|
|2006||Awano, T., Katz, ML., O'Brien, DP., Taylor, JF., Evans, J., Khan, S., Sohar, I., Lobel, P., Johnson, GS. :|
|A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid lipofuscinosis. Mol Genet Metab 87:341-8, 2006. Pubmed reference: 16386934. DOI: 10.1016/j.ymgme.2005.11.005.|
|2005||Evans, J., Katz, ML., Levesque, D., Shelton, GD., de Lahunta, A., O'Brien, D. :|
|A variant form of neuronal ceroid lipofuscinosis in American bulldogs. J Vet Intern Med 19:44-51, 2005. Pubmed reference: 15715047.|
|Wöhlke, A., Distl, O., Drögemüller, C. :|
|The canine CTSD gene as a candidate for late-onset neuronal ceroid lipofuscinosis. Anim Genet 36:530-2, 2005. Pubmed reference: 16293139. DOI: 10.1111/j.1365-2052.2005.01375.x.|
- Created by Frank Nicholas on 26 Oct 2010
- Changed by Vicki Meyers-Wallen on 18 Sep 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Tosso Leeb on 28 May 2013