OMIA:002105-9615 : Neuroaxonal dystrophy, PLA2G6-related in Canis lupus familiaris

In other species: sheep

Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 256600 (trait) , 610217 (trait) , 612953 (trait) , 603604 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Molecular basis: Tsuboi et al. (2017): PLA2G6 c.1579G>A; p.T526A

Pathology: Tsuboi et al. (2017): this disorder is "histopathologically characterized by severe axonal swelling, known as “spheroids,” throughout the nervous system."

Prevalence: Raj and Giger (2020): "Archived samples from Papillons clinically diagnosed with NAD prior to 2015 as well as samples obtained from 660 Papillons from North America and Europe between 2015 and 2017 were screened for the presence of this PLA2G6 gene variant (XM_022424454.1:c.1579G > A) ... .17.5% of the 660 tested Papillons were heterozygotes, resulting in a variant allele frequency of 0.092 in this initial survey. Since then, screening for NAD in Papillons by at least 10 other laboratories and data from the Health Committee of Papillon Club of America gathered between 2017 and 2019 reveal a variant allele frequency of 0.047."

Breed: Papillon.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
PLA2G6 phospholipase A2, group VI (cytosolic, calcium-independent) Canis lupus familiaris 10 NC_051814.1 (27290620..27351106) PLA2G6 Homologene, Ensembl , NCBI gene


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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
113 Papillon Neuroaxonal dystrophy, PLA2G6-related PLA2G6 missense Naturally occurring variant CanFam3.1 10 g.26544820G>A c.1579G>A p.(T527A) 2017 28107443 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 Raj, K., Giger, U. :
Initial survey of PLA2G6 missense variant causing neuroaxonal dystrophy in Papillon dogs in North America and Europe. Canine Med Genet 7:17, 2020. Pubmed reference: 33292730 . DOI: 10.1186/s40575-020-00098-4.
2017 Tsuboi, M., Watanabe, M., Nibe, K., Yoshimi, N., Kato, A., Sakaguchi, M., Yamato, O., Tanaka, M., Kuwamura, M., Kushida, K., Ishikura, T., Harada, T., Chambers, J.K., Sugano, S., Uchida, K., Nakayama, H. :
Identification of the PLA2G6 c.1579G>A missense mutation in Papillon dog neuroaxonal dystrophy using whole exome sequencing analysis. PLoS One 12:e0169002, 2017. Pubmed reference: 28107443 . DOI: 10.1371/journal.pone.0169002.
2009 Nibe, K., Nakayama, H., Uchida, K. :
Immunohistochemical features of dystrophic axons in Papillon dogs with neuroaxonal dystrophy. Vet Pathol 46:474-83, 2009. Pubmed reference: 19176506 . DOI: 10.1354/vp.08-VP-0156-U-FL.
2007 Diaz, JV., Duque, C., Geisel, R. :
Neuroaxonal dystrophy in dogs: case report in 2 litters of Papillon puppies. J Vet Intern Med 21:531-4, 2007. Pubmed reference: 17552463 .
Nibe, K., Kita, C., Morozumi, M., Awamura, Y., Tamura, S., Okuno, S., Kobayashi, T., Uchida, K. :
Clinicopathological features of canine neuroaxonal dystrophy and cerebellar cortical abiotrophy in Papillon and Papillon-related dogs. J Vet Med Sci 69:1047-52, 2007. Pubmed reference: 17984592 .
Tamura, S., Tamura, Y., Uchida, K. :
Magnetic resonance imaging findings of neuroaxonal dystrophy in a papillon puppy. J Small Anim Pract 48:458-61, 2007. Pubmed reference: 17543020 . DOI: 10.1111/j.1748-5827.2006.00304.x.
1995 Franklin, R.J.M., Jeffery, N.D., Ramsey, I.K. :
Neuroaxonal dystrophy in a litter of papillon pups Journal of Small Animal Practice 36:441-444, 1995. Pubmed reference: 8583759 .

Edit History

  • Created by Frank Nicholas on 12 May 2017
  • Changed by Frank Nicholas on 12 May 2017
  • Changed by Imke Tammen2 on 09 Apr 2021