OMIA:001505-9615 : Neuronal ceroid lipofuscinosis, 10 in Canis lupus familiaris (dog)

In other species: sheep

Categories: Lysosomal storage disease , Nervous system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 610127 (trait) , 116840 (gene)

Links to MONDO diseases:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2006

Cross-species summary: One of several variants of neuronal ceroid lipofuscinosis (NCL) or Batten disease: CLN10; NCL10

Species-specific description: The neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases characterized by intraneuronal accumulation of fluorescent granules and early neuronal death. Onset is usually before 2 years of age, with death by 7 years of age. Unlike other forms of NCL, dogs with NCL10 do not show signs of cerebral dysfunction or blindness. A genetic test is available.

Mapping: CFA18

Molecular basis: The causative variant is a c.597G>A transition in exon 5 of the CTSD gene leading to p.M199I in the encoded cathepsin D (Awano et al., 2006). Cathepsin D-specific activity in affected dogs is approximately 36% of normal.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

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 (Dog) (VBO_0200034).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

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

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
66 American Bulldog (Dog) Neuronal ceroid lipofuscinosis, 10 CTSD missense Naturally occurring variant CanFam3.1 18 g.46013354C>T c.597G>A p.(M199I) 2006 16386934 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2013). OMIA:001505-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2023 Stee, K., Van Poucke, M., Lowrie, M., Van Ham, L., Peelman, L., Olby, N., Bhatti, S.F.M. :
Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med 37:1306-1322, 2023. Pubmed reference: 37341581. DOI: 10.1111/jvim.16742.
2021 Cerda-Gonzalez, S., Packer, R.A., Garosi, L., Lowrie, M., Mandigers, P.J.J., O'Brien, D.P., Volk, H.A. :
International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification. J Vet Intern Med 35:1218-1230, 2021. Pubmed reference: 33769611. DOI: 10.1111/jvim.16108.
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 108:277-87, 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.

Edit History


  • 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