OMIA 002591-9615 : Lysosomal storage disease, CNP-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 619071 (gene) , 123830 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal incomplete dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2022

Species-specific description: Bullock et al. (2022) report a progressive neurological disorder in purebred Dalmatian dogs with similarities to the neuronal ceroid lipofuscinoses.

Molecular basis: Bullock et al. (2022): “ Whole genome sequences, generated with DNA from the two euthanized Dalmatians, both contained a rare, homozygous single-base deletion and reading-frame shift in CNP … . The late-onset disease was exhibited by five of seven related Dalmatians that were heterozygous for the deletion allele and over 8 years of age, whereas none of 16 age-matched reference-allele homozygotes developed neurologic signs.”

Clinical features: Bullock et al. (2022): “The disease is characterized by anxiety, pacing and circling, hypersensitivity, cognitive decline, sleep disturbance, loss of coordination, loss of control over urination and defecation, and visual impairment. Neurological signs first became apparent when the dogs were approximately 18 months of age and progressed slowly. Two affected littermates were euthanized at approximately 7 years, 5 months and 8 years, 2 months of age due to the severity of neurological impairment. The mother of the affected dogs and four other relatives exhibited milder, later-onset neurological signs.”

Pathology: Bullock et al. (2022): “Pronounced accumulations of autofluorescent intracellular inclusions were found in cerebral cortex, cerebellum, optic nerve, and cardiac muscle of the affected dogs. These inclusions co-localized with immunolabeling of the lysosomal marker protein LAMP2 and bound antibodies to mitochondrial ATPase subunit c, indicating that the dogs suffered from a lysosomal storage disease with similarities to the neuronal ceroid lipofuscinoses. Ultrastructural analysis indicated that the storage bodies were surrounded by a single-layer membrane, but the storage granules were distinct from those reported for other lysosomal storage diseases.”

Breed: Dalmatian.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CNP 2',3'-cyclic nucleotide 3' phosphodiesterase Canis lupus familiaris 9 NC_051813.1 (21614689..21606902) CNP Homologene, Ensembl, NCBI gene

Variants

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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
1502 Dalmatian Lysosomal storage disease, CNP-related CNP deletion, small (<=20) Naturally occurring variant Dog10K_Boxer_Tasha 9 g.20350240del c.1107del p.(K370Nfs*11) ENSCAFT00000102206 2022 35447247

Reference


2022 Bullock, G., Johnson, G.S., Mhlanga-Mutangadura, T., Petesch, S.C., Thompson, S., Goebbels, S., Katz, M.L. :
Lysosomal storage disease associated with a CNP sequence variant in Dalmatian dogs. Gene 830:146513, 2022. Pubmed reference: 35447247. DOI: 10.1016/j.gene.2022.146513.

Edit History


  • Created by Imke Tammen2 on 15 Nov 2022
  • Changed by Imke Tammen2 on 15 Nov 2022