OMIA 001428-9615 : Trapped Neutrophil Syndrome in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 216550 (trait) , 607817 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific symbol: TNS

Molecular basis: Starting with a list of candidate genes based on comparative clinical signs in other species (especially humans), Shearman and Wilton (2011) used linkage analysis to eventually narrow the field down to the VPS13B gene. They "sequenced each of the 63 exons of VPS13B in affected and control dogs and found that the causative mutation in Border collies is a 4 bp deletion in exon 19 of the largest transcript that results in premature truncation of the protein."

Clinical features: Affected dogs present with fever, gastrointestinal signs, polyarthritis, joint effusion, and lameness and failure to thrive between 6 and 12 weeks of age and have a characteristic ‘ferret-like’ elongated face (Allen et al., 1996; Shearman & Wilton, 2011; Mizukami et al., 2012; Mason et al., 2014; Hegler et al., 2020). Proprioception and placing and hopping reflexes were markedly reduced, while skin reflex and deep pain sensations were normal (Mizukami et al., 2012). Decreased level of consciousness, astasia, and incontinence were also reported by Mizukami et al. (2012). Ill thrift and continued recurrent/chronic infections are hallmark features (Hegler et al., 2020). Dogs are commonly dying or being euthanised by one year of age (Wouda et al. 2010).

[IT thanks DVM students Laura Sweeting and Tracy Yeung, who provided the basis of this contribution in April 2022]

Pathology: Hegler et al. (2020) and Mizukami et al. (2013) discuss trapped neutrophil syndrome as a condition characterised by retention of neutrophils in the bone marrow of Border Collies. Whilst understanding of pathophysiological mechanisms is incomplete, neutrophils are seen to move inadequately from their haemopoietic site in bone marrow, to peripheral circulation (Mizukami et al., 2012).

The two major features are reduced circulating neutrophil numbers (peripheral neutropoenia) and intramedullary myeloid hyperplasia (Mason et al., 2014). Eosinophilia, monocytosis, hypercholesterolaemia and nRBC in circulation and non-regenerative anaemia are reported (Mizukami et al., 2013).

Radiographs showed capsular joint swelling and heterogeneous metaphyseal radiolucencies in multiple joints and cytology revealed non-degenerate neutrophilic inflammation in multiple joints (Hegler et al., 2020).

[IT thanks DVM students Laura Sweeting and Tracy Yeung, who provided the basis of this contribution in April 2022]

Prevalence: Mizukami et al. (2016) reported the frequency of the 4bp deletion allele as 0.059 in 500 Border collies in Japan.

Breed: Border Collie.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
VPS13B vacuolar protein sorting 13 homolog B (yeast) Canis lupus familiaris 13 NC_051817.1 (1253509..1988060) VPS13B 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
478 Border Collie Trapped Neutrophil Syndrome VPS13B deletion, small (<=20) Naturally occurring variant CanFam3.1 13 g.1412654_1412657del c.2893_2896del p.(V595Ifs) XM_539102.7; XP_539102.2; published as g.4411950_4411953del GTTT (HM036106.1). BLAST of published sequence (HM036106.1) identified genomic position in CanFam3.1 as g.1412654_1412657del 2011 21605373

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.
2021 Soh, P.X.Y., Hsu, W.T., Khatkar, M.S., Williamson, P. :
Evaluation of genetic diversity and management of disease in Border Collie dogs. Sci Rep 11:6243, 2021. Pubmed reference: 33737533. DOI: 10.1038/s41598-021-85262-x.
2020 Hegler, A.K., Grooters, A.M., Dehghanpir, S.D., Gallaher, R.A., Gaschen, L.E. :
Trapped neutrophil syndrome in a Border Collie. J Am Anim Hosp Assoc 56:e56304, 2020. Pubmed reference: 32182118. DOI: 10.5326/JAAHA-MS-6981.
2016 Mizukami, K., Yabuki, A., Kohyama, M., Kushida, K., Rahman, M.M., Uddin, M.M., Sawa, M., Yamato, O. :
Molecular prevalence of multiple genetic disorders in Border collies in Japan and recommendations for genetic counselling. Vet J 214:21-3, 2016. Pubmed reference: 27387721. DOI: 10.1016/j.tvjl.2016.05.004.
2014 Mason, S.L., Jepson, R., Maltman, M., Batchelor, D.J. :
Presentation and management of trapped neutrophil syndrome (TNS) in UK Border collies. J Small Anim Pract 55:57-60, 2014. Pubmed reference: 24032537. DOI: 10.1111/jsap.12134.
2013 Mizukami, K., Yabuki, A., Kawamichi, T., Chang, H.S., Rahman, M.M., Uddin, M.M., Kohyama, M., Yamato, O. :
Real-time PCR genotyping assay for canine trapped neutrophil syndrome and high frequency of the mutant allele in Border collies. Vet J 195:260-1, 2013. Pubmed reference: 22795605. DOI: 10.1016/j.tvjl.2012.06.014.
2012 Mizukami, K., Shoubudani, T., Nishimoto, S., Kawamura, R., Yabuki, A., Yamato, O. :
Trapped neutrophil syndrome in a Border Collie dog: clinical, clinico-pathologic, and molecular findings. J Vet Med Sci 74:797-800, 2012. Pubmed reference: 22240985. DOI: 10.1292/jvms.11-0472.
2011 Shearman, JR., Wilton, AN. :
A canine model of Cohen syndrome: trapped neutrophil syndrome. BMC Genomics 12:258, 2011. Pubmed reference: 21605373. DOI: 10.1186/1471-2164-12-258.
2010 Wouda; R.M., King, T.J., Mackay, B.M. :
Long-term management of trapped neutrophil syndrome in two Border Collies. Australian Veterinary Practitioner 40:58-63, 2010.
2007 Shearman, JR., Wilton, AN. :
Elimination of neutrophil elastase and the genes for [corrected] adaptor protein complex 3 subunits [corrected] as the cause of trapped neutrophil syndrome in Border collies. Anim Genet 38:188-9, 2007. Pubmed reference: 17302793. DOI: 10.1111/j.1365-2052.2007.01565.x.
2006 Shearman, JR., Zhang, QY., Wilton, AN. :
Exclusion of CXCR4 as the cause of trapped neutrophil syndrome in Border Collies using five microsatellites on canine chromosome 19. Anim Genet 37:89, 2006. Pubmed reference: 16441310. DOI: 10.1111/j.1365-2052.2005.01413.x.
1996 Allan, F.J., Thompson, K.G., Jones, B.R., Burbidge, H.M., Mckinley, R.L. :
Neutropenia with a probable hereditary basis in Border Collies. New Zealand Veterinary Journal 44:67-72, 1996. Pubmed reference: 16031897. DOI: 10.1080/00480169.1996.35937.

Edit History


  • Created by Frank Nicholas on 30 May 2011
  • Changed by Frank Nicholas on 29 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 18 Oct 2016
  • Changed by Imke Tammen2 on 26 Jan 2022
  • Changed by Imke Tammen2 on 22 Apr 2022
  • Changed by Imke Tammen2 on 23 Apr 2022