Trapped neutrophil syndrome

From Dog

Trapped neutrophil syndrome is an autosomal-recessive genetic disease of the Border Collie[1] characterized by severe neutropenia.

The disease, which is similar to Cohen syndrome in humans, is caused by a mutation in the canine VPS13B gene and was originally described in the Australian and New Zealand population of Border collies characterised by a deficiency of segmented neutrophils in the blood and hyperplasia of myeloid cells in the bone marrow[2].

This syndrome has been traced back to a single common ancestor suggesting that the disease was the result of a single mutational event that had been spread through the population by the champion sire effect[3]. If the mutation predates development of the breed it may exist in other collie breeds, as does Collie eye anomaly[4].

Severely affected pups show abnormal craniofacial development with a narrowed elongated skull shape described by breeders as ferret-like. Affected pups are often smaller than their litter mates and suffer from chronic infections and failure to thrive resulting from a compromised immune system[5] as well as varying degrees of mental retardation[6].

Some show early infections from six weeks of age. For others the first sign of TNS is a bad reaction to immunisation at 12 weeks, while in a few cases clinical signs are very mild and not recognised until two or more years of age.

A diagnosis can be difficult without PCR testing and this syndrome should be differentiated from cyclic neutropenia of Collie breeds and other causes of neutropenia.

A PCR-based assay is currently available for this disease.

Many dogs succumb to the disease at an early age.

References

  1. Mizukami K et al (2012) Trapped neutrophil syndrome in a Border Collie dog: clinical, clinico-pathologic, and molecular findings. J Vet Med Sci 74(6):797-800
  2. Allan, FJ et al (1996) Neutropenia with a probable hereditary basis in Border Collies. N Z Vet J 44:67–72
  3. Shearman JR et al (2006) Exclusion of CXCR4 as the cause of Trapped Neutrophil Syndrome in Border collies using five microsatellites on canine chromosome 19. Anim Genet '37:89
  4. Parker HG et al (2007) Breed relationships facilitate fine-mapping studies: a 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds. Genome Res 17:1562–1571
  5. Shearman JR & Wilton AN (2007) Elimination of neutrophil elastase and adaptor protein complex 3 subunit genes as the cause of trapped neutrophil syndrome in Border collies. Anim Genet 38:188–189
  6. Shearman JR et al (2011) A canine model of Cohen syndrome: Trapped Neutrophil Syndrome. BMC Genomics 12:258