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

In other species: sheep

Possibly relevant human trait(s) and/or gene(s) (MIM number): 610127

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2006

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.

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_006600.3 (46019457..46010440) CTSD Homologene, Ensembl, NCBI gene

Variants

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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
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

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 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.

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