OMIA:002119-9615 : Polyneuropathy, GJA9-related in Canis lupus familiaris (dog)
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 611923 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal incomplete dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2017
Species-specific symbol: LPN2
History: Variants in other genes have been associated with other forms of polyneuropathy and/or laryngeal paralysis in various breeds: OMIA 001917-9615 (ARHGEF10), OMIA 002222-9615 (RAPGEF6), OMIA 001970-9615 (RAB3GAP1), OMIA 002284-9615 (SBF2), OMIA 002301-9615 (CNTNAP1). References relating to polyneuropathies and laryngeal paralysis in dogs without known genetic associations are listed under OMIA 001292-9615 and OMIA 001206-9615, respectively.
Mapping: Becker et al. (2017): "A genome-wide comparison of 173 k SNP genotypes of 176 cases, excluding dogs homozygous for the ARHGEF10 variant, and 138 controls, was carried out to detect further PN-associated variants. A single suggestive significant association signal on CFA15 was found. "
Molecular basis: Becker et al. (2017) identified a likely causal variant as a "GJA9 variant (CanFam3.1: chr15.3863,524_3863,525delAG) [which] results in a frameshift (ENSCAFT00000038555: c.1107_1108delAG) and premature stop codon (F1PSG8_CANLF: p.Glu370AsnfsTer12) that is predicted to truncate almost half of the intracellular C-terminus of the encoded connexin."
Have human generated variants been created, e.g. through genetic engineering and gene editing
Pathology: Becker et al. (2017): "Resin sections from the peroneal nerve were qualitatively evaluated from 5 Leonberger dogs with PN [polyneuropathy] and the GJA9 variant .... The prominent pathologic abnormality was variably severe nerve fiber loss resulting from chronic axonal degeneration .... Large nerve fiber loss was most prominent with an increased population of small caliber nerve fibers."
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|GJA9||gap junction protein, alpha 9, 59kDa||Canis lupus familiaris||15||NC_051819.1 (3983099..3985924)||GJA9||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|
|794||Leonberger||Polyneuropathy (LPN2)||GJA9||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||15||g.3863524_3863525del||c.1107_1108delAG||p.(A370Nfs*12)||2017||28841859|
Cite this entry
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||Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. :|
|Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7.|
|2017||Becker, D., Minor, K.M., Letko, A., Ekenstedt, K.J., Jagannathan, V., Leeb, T., Shelton, G.D., Mickelson, J.R., Drögemüller, C. :|
|A GJA9 frameshift variant is associated with polyneuropathy in Leonberger dogs. BMC Genomics 18:662, 2017. Pubmed reference: 28841859. DOI: 10.1186/s12864-017-4081-z.|
|2011||Granger, N. :|
|Canine inherited motor and sensory neuropathies: an updated classification in 22 breeds and comparison to Charcot-Marie-Tooth disease. Vet J 188:274-85, 2011. Pubmed reference: 20638305. DOI: 10.1016/j.tvjl.2010.06.003.|
- Created by Frank Nicholas on 28 Aug 2017
- Changed by Frank Nicholas on 01 Sep 2017
- Changed by Imke Tammen2 on 11 Dec 2020
- Changed by Imke Tammen2 on 11 Jul 2021