OMIA 001443-9615 : Neuronal ceroid lipofuscinosis, 6 in Canis lupus familiaris

In other species: sheep

Possibly relevant human trait(s) and/or gene(s) (MIM number): 601780

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

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. Dogs with NCL6 have early-onset, progressive disease that results in blindness and premature death. A genetic test is available.

Mapping: CFA30

Molecular basis: The causative variant is a c.829T>C transition in exon 7 of CLN6 leading to p.W277R on the protein level (Katz et al., 2011). Affected dogs have CLN6 deficiency. The function of CLN6 is unknown, but is likely an intrinsic membrane protein with 7 transmembrane domains (Katz et al., 2011).

Clinical features: Affected dogs present with visual deficits which progress to complete blindness, as well as progressive anxiety, cognitive and motor degeneration, circling, and incoordination (Katz et al., 2011).

Pathology: Cerebellar hypoplasia and enlarged lateral ventricles are present. Large amounts of autofluorescent substance are present in the retina, cerebral cortex, and cerebellum, which is most prevalent in the cerebellar Purkinje and granular layers and the retinal ganglion cell layer (Katz et al., 2011).

Prevalence: The prevalence of this condition appears to be very low, as only two affected dogs have been definitively identified thus far (Katz et al., 2011).

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

Genetic testing: A genetic test is available.

Breed: Australian Shepherd.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CLN6 ceroid-lipofuscinosis, neuronal 6, late infantile, variant Canis lupus familiaris 30 NC_006612.3 (32264251..32246394) CLN6 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 required column headers

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
Australian Shepherd Neuronal ceroid lipofuscinosis, 6 CLN6 missense CanFam3.1 30 g.32247875 c.829T>C p.W277R 2011 21234413 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.
2011 Katz, ML., Farias, FH., Sanders, DN., Zeng, R., Khan, S., Johnson, GS., O'Brien, DP. :
A missense mutation in canine CLN6 in an Australian shepherd with neuronal ceroid lipofuscinosis. J Biomed Biotechnol 2011:198042, 2011. Pubmed reference: 21234413. DOI: 10.1155/2011/198042.
2010 Bellettato, C.M., Scarpa, M. :
Pathophysiology of neuropathic lysosomal storage disorders. J Inherit Metab Dis 33:347-62, 2010. Pubmed reference: 20429032. DOI: 10.1007/s10545-010-9075-9.
2008 O'Brien, DP., Katz, ML. :
Neuronal ceroid lipofuscinosis in 3 Australian shepherd littermates. J Vet Intern Med 22:472-5, 2008. Pubmed reference: 18371036. DOI: 10.1111/j.1939-1676.2008.0079.x.

Edit History


  • Created by Frank Nicholas on 13 Jul 2011
  • Changed by Vicki Meyers-Wallen on 18 Sep 2011
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Tosso Leeb on 28 May 2013