OMIA 002119-9615 : Polyneuropathy, GJA9-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 611923 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Incompletely 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."

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."

Breed: Leonberger.

Associated gene:

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

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 second, third etc relevant column headers.

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

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 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.

Edit History


  • 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