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Trapped Neutrophil Syndrome (TNS): Border Collie, Huntaway and New Zealand Heading Dog

Hematológico · Dog

Trapped neutrophil syndrome (TNS) is an inherited haematological disease described in the Border Collie and in the New Zealand working breeds Huntaway and New Zealand Heading Dog. Neutrophils mature in the bone marrow but cannot leave it (they remain 'trapped'), so the blood shows neutropenia while the marrow is hyperplastic. The result is an impaired immune system with recurrent infections in puppies, of highly variable severity. DNA testing identifies carriers and makes it possible to eliminate the disease from working lines.
Inheritance patternAutosomal recessive (monogenic disease; both parents of an affected animal are obligate carriers).
Gene / MutationVPS13B (CFA13), exon 19: 4 bp deletion, CanFam3.1 g.1412654_1412657del; c.2893_2896del; p.(V965Ifs). Note: the previous annotation p.(V595Ifs) was incorrect and was corrected by OMIA (2026).
PenetranceVariable in homozygotes: the age of onset and the severity differ greatly between affected animals, and dogs with the mutation in both alleles and minimal signs have been described. Heterozygotes are healthy.
Codeeubx
Turnaround time7 days
Price52,72 €

Incidence

Described in the working Border Collie and in the Huntaway and New Zealand Heading Dog. In Border Collies from Thailand a carrier prevalence of 4 % was found (allele frequency of 2 %). Outside those populations the data are scarce (limited data). Carrier testing has substantially reduced cases.

Breeder management

- Test the breeding animals of the working Border Collie and of the New Zealand working breeds before the first mating\n- Never mate carrier with carrier: 25 % risk of affected puppies\n- A carrier can be mated with a clear animal, prioritising clear offspring to eliminate the allele from the line\n- Suspect TNS in puppies with repeated infections and neutropenia: request genetic testing and a bone marrow examination\n- Report the results to the breed club, especially in working populations with low genetic variability

Specialist notes

The differential diagnosis of chronic neutropenia in the puppy includes viral infections (parvovirus, distemper), immune and drug-induced neutropenias, and cyclic haematopoiesis. The laboratory key to TNS is the combination of persistent neutropenia with myeloid hypercellularity in the marrow (myelopoiesis without release). Treatment of affected animals is supportive (antibiotics for intercurrent infections) and the prognosis depends on severity; the biochemical profile is usually normal unless there is active infection. As in any recessive disease, both parents of an affected animal are obligate carriers.

References

1. Shearman JR, Wilton AN. A canine model of Cohen syndrome: Trapped Neutrophil Syndrome. BMC Genomics. 2011;12:258. PMID: 21605373
2. Mizukami K, et al. Trapped neutrophil syndrome in a Border Collie dog: clinical, clinico-pathologic, and molecular findings. J Vet Med Sci. 2012;74(6):797-800. PMID: 22240985
3. Lerdkrai C, Phungphosop N. Multiplex allele-specific polymerase chain reaction-based prevalence study of canine trapped neutrophil syndrome in Thailand. Vet World. 2023;16(11):2271-2276. PMID: 38152268

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