Test Detail
Gray Collie Syndrome (Canine Cyclic Neutropenia)
Hematológico · Dog
Gray collie syndrome (gray collie) or canine cyclic hematopoiesis is a lethal genetic disease in which the bone marrow produces blood cells in cycles of approximately 12 days, with periodic drops in neutrophils. Affected puppies are born with a silver or dilute gray coat and suffer recurrent severe infections synchronized with the neutrophil valleys. Most die or are euthanized in the first months of life. DNA testing identifies carriers that are normal in appearance and health.
Incidence
Very rare disease at present. Classically described in the Collie («gray collie»/cyclic hematopoiesis), but also documented in the Basset Hound and in mixed-breed dogs; the variant is not restricted to the Collie. The Border Collie has a different hereditary neutropenia (trapped neutrophil syndrome, another gene). There are no reliable current carrier figures (limited data). Sources: OMIA:000248-9615; Benson 2003 (PMID 12897784); Lee 2022 (PMID 35904319).
Breeder management
- Test breeding animals from collie lines with a history of gray puppies or recurrent neonatal infections
- Never mate carrier with carrier: 25% risk of affected puppies
- A carrier can be mated to a clear animal, keeping only clear offspring for breeding if you seek to eliminate the allele
- Both parents of an affected gray puppy are obligate carriers: inform the owners of related litters
- The dilute gray color in a collie puppy is an immediate warning sign: confirm with a test and hematological study
- Never mate carrier with carrier: 25% risk of affected puppies
- A carrier can be mated to a clear animal, keeping only clear offspring for breeding if you seek to eliminate the allele
- Both parents of an affected gray puppy are obligate carriers: inform the owners of related litters
- The dilute gray color in a collie puppy is an immediate warning sign: confirm with a test and hematological study
Specialist notes
Diagnosis relies on serial complete blood counts every 2-3 days demonstrating the cyclic oscillation of neutrophils (approximate cycle of 12 days, shorter than that of classic human cyclic neutropenia). Differential diagnosis with immune, infectious and pharmacological neutropenias, and with trapped neutrophil syndrome of the Border Collie. Treatment (antibiotics during the valleys, supportive care, and in selected cases colony-stimulating factors under specialist control) prolongs survival but rarely offers acceptable long-term quality of life.
References
1. Benson KF, Li FQ, Person RE, et al. Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase. Nat Genet 2003;35(1):90-6. PMID: 12897784
2. Benson KF, Person RE, Li FQ, et al. Paradoxical homozygous expression from heterozygotes and heterozygous expression from homozygotes through a polyadenine tract in the AP3B1 gene responsible for canine cyclic neutropenia. Nucleic Acids Res 2004;32(21):6327-33. PMID: 15576359
3. Lee GKC, Barbosa C, Andersen G, et al. Cyclic hematopoiesis in a mixed-breed dog: case report and brief review. J Vet Diagn Invest 2022;34(6):1006-9. PMID: 35904319
4. OMIA:000248-9615 (AP3B1). https://omia.org/OMIA000248/9615/
2. Benson KF, Person RE, Li FQ, et al. Paradoxical homozygous expression from heterozygotes and heterozygous expression from homozygotes through a polyadenine tract in the AP3B1 gene responsible for canine cyclic neutropenia. Nucleic Acids Res 2004;32(21):6327-33. PMID: 15576359
3. Lee GKC, Barbosa C, Andersen G, et al. Cyclic hematopoiesis in a mixed-breed dog: case report and brief review. J Vet Diagn Invest 2022;34(6):1006-9. PMID: 35904319
4. OMIA:000248-9615 (AP3B1). https://omia.org/OMIA000248/9615/