OMIA:002032-9615 : Neuropathy, sensory, RETREG1-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 613115 (trait) , 613114 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

Species-specific name: Sensory neuropathy; hereditary sensory and autonomic neuropathy

Species-specific symbol: SN; HSAN

Molecular basis: Forman et al. (2016): "6.47 Mb inversion was identified with breakpoints in intron 3 of FAM134B (chr4:86,910,352) and in an upstream intergenic region (chr4:80,439,639) . . . All three cases were homozygous for the inversion and all 170 controls homozygous for the reference allele." Amengual-Batle et al. (2018) reported the same variant in two affected mixed-breed dogs. Gutierrez-Quintana et al. (2021): "Whole genome sequencing identified a missense variant in the RETREG1 [also called Fam134B] (reticulophagy regulator 1) gene (c.656C > T, p.P219L). All [three] affected [mixed breed] dogs were homozygous for the variant, which was not detected in 1193 dogs from different breeds."

Clinical features: Forman et al. (2106): " Clinical signs start between two and seven months of age and include progressive proprioceptive ataxia with intermittent knuckling of the paws, hyperextension of the limbs, and self-mutilation wounds in the distal part of the limbs . . . . Usually, the pelvic limbs are more severely affected than the thoracic limbs. There is decreased or loss of proprioception and nociception in all limbs, and in some cases autonomic signs such as urinary incontinence and in the later stage regurgitation has also been reported (Vermeersch et al. 2005). Electrophysiological studies show decreased or absent sensory nerve compound action potentials, normal or reduced motor nerve conduction velocities and normal electromyography in the appendicular muscles." Gutierrez-Quintana et al. (2021): "Five related mixed breed puppies from 2 litters were presented over a 2-year period ... . All had a previous history of severe mutilation of the distal pelvic limbs and chronic progressive pelvic limb gait abnormalities. ... Electrodiagnostic testing was performed ... and abnormalities were limited to the absence of sensory nerve action potentials (SNAP) during sensory nerve stimulation."

Pathology: Gutierrez-Quintana et al. (2021): "No macroscopic changes were observed. Histopathological abnormalities were limited to the peripheral nerves, dorsal root ganglia, and autonomic ganglia. Nerve histology indicated moderate myelinated fiber loss and axonal features compatible with Wallerian degeneration with some dystrophic changes."

Breeds: Border Collie (Dog) (VBO_0200193), Mixed Breed (Dog) (VBO_0200902).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
FAM134B family with sequence similarity 134, member B Canis lupus familiaris 4 NC_051808.1 (87442470..87564197) FAM134B Homologene, Ensembl , NCBI gene


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 Year Published PubMed ID(s) Acknowledgements
752 Border Collie (Dog) Mixed Breed (Dog) Neuropathy, sensory FAM134B inversion Naturally occurring variant CanFam3.1 4 g.80439639_86910352inv "6.47 Mb inversion was identified with breakpoints in intron 3 of FAM134B (chr4:86,910,352) and in an upstream intergenic region (chr4:80,439,639) ... … Analysis of RNAseq data revealed FAM134B was majorly disrupted by the inversion, with novel exons occurring 3′ of the final normally transcribed exon before the inversion, due to cryptic splicing." 2016 27527794
1342 Mixed Breed (Dog) Neuropathy, sensory FAM134B missense Naturally occurring variant CanFam3.1 4 g.86916562C>T c.656C>T p.(P219L) NM_001314111.1; NP_001301040.1 2021 34387380

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002032-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2021 Gutierrez-Quintana, R., Mellersh, C., Wessmann, A., Ortega, M., Penderis, J., Sharpe, S., Freeman, E., Stevenson, L., Burmeister, L. :
Hereditary sensory and autonomic neuropathy in a family of mixed breed dogs associated with a novel RETREG1 variant. J Vet Intern Med 35:2306-2314, 2021. Pubmed reference: 34387380. DOI: 10.1111/jvim.16242.
2019 Correard, S., Plassais, J., Lagoutte, L., Botherel, N., Thibaud, J.L., Hédan, B., Richard, L., Lia, A.S., Delague, V., Mège, C., Mathis, S., Guaguère, E., Paradis, M., Vallat, J.M., Quignon, P., André, C. :
Canine neuropathies: powerful spontaneous models for human hereditary sensory neuropathies. Hum Genet 138:455-466, 2019. Pubmed reference: 30955094. DOI: 10.1007/s00439-019-02003-x.
2018 Amengual-Batle, P., Rusbridge, C., José-López, R., Golini, L., Shelton, G.D., Mellersh, C.S., Gutierrez-Quintana, R. :
Two mixed breed dogs with sensory neuropathy are homozygous for an inversion disrupting FAM134B previously identified in Border Collies. J Vet Intern Med 32:2082-2087, 2018. Pubmed reference: 30307654. DOI: 10.1111/jvim.15312.
2016 Forman, O.P., Hitti, R.J., Pettitt, L., Jenkins, C.A., O'Brien, D.P., Shelton, G.D., De Risio, L., Quintana, R.G., Beltran, E., Mellersh, C. :
An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed. G3 (Bethesda) 6:2687-92, 2016. Pubmed reference: 27527794. DOI: 10.1534/g3.116.027896.
2013 Tsuboi, M., Uchida, K., Ide, T., Ogawa, M., Inagaki, T., Tamura, S., Saito, M., Chambers, J.K., Nakayama, H. :
Pathological features of polyneuropathy in three dogs. J Vet Med Sci 75:327-35, 2013. Pubmed reference: 23123885.
2005 Harkin, KR., Cash, WC., Shelton, GD. :
Sensory and motor neuropathy in a Border Collie. J Am Vet Med Assoc 227:1263-5, 1250, 2005. Pubmed reference: 16266014.
Vermeersch, K., Van Ham, L., Braund, KG., Bhatti, S., Tshamala, M., Chiers, K., Schrauwen, E. :
Sensory neuropathy in two Border Collie puppies. J Small Anim Pract 46:295-9, 2005. Pubmed reference: 15971901.
1992 Franklin, R.J.M., Olby, N.J., Targett, M.P., Houlton, J.E.F. :
Sensory neuropathy in a Jack Russell terrier. J Small Anim Pract 33:402-404, 1992. DOI:
1987 Wheeler, S.J. :
Sensory neuropathy in a Border Collie puppy. Journal of Small Animal Practice 28:281-289, 1987.
1982 Duncan, I.D., Griffiths, I.R., Munz, M. :
The pathology of a sensory neuropathy affecting Long Haired Dachshund dogs. Acta Neuropathol 58:141-51, 1982. Pubmed reference: 6295050. DOI: 10.1007/BF00691655.

Edit History

  • Created by Frank Nicholas on 20 Aug 2016
  • Changed by Frank Nicholas on 20 Aug 2016
  • Changed by Frank Nicholas on 28 Mar 2019
  • Changed by Frank Nicholas on 12 Sep 2020
  • Changed by Frank Nicholas on 08 Feb 2021
  • Changed by Imke Tammen2 on 16 Aug 2021
  • Changed by Imke Tammen2 on 26 Aug 2023