Canine Leukocyte Adhesion Deficiency (CLAD) in Irish Setters
Canine leukocyte adhesion deficiency, Type I (CLAD-Type I) is an inherited blood disorder affecting Irish Setters. It is characterized by abnormal blood clotting and immune system functions.
Phenotype: Affected Irish Setters have abnormal blood clotting and immune system functions and may present with lameness, recurrent skin infections, bone infections, and gingivitis. Irish Setter pups may exhibit umbilical vein infection, swollen or inflamed lymph nodes, and a failure to gain weight. Although some dogs can live for years with this condition, most affected dogs die early.
Breeds appropriate for testing: Irish Setter, Irish Red and White Setter
Explanation of Results:
Dogs with N/N genotype will not have canine leukocyte adhesion deficiency and cannot transmit this variant to their offspring.
Dogs with N/CLADis genotype will not have canine leukocyte adhesion deficiency, but are carriers. They will transmit this CLAD variant to 50% of their offspring. Matings between two carriers are predicted to produce 25% canine leukocyte adhesion deficiency-affected puppies.
Dogs with CLADis/CLADis genotype will have canine leukocyte adhesion deficiency, a potentially fatal condition.
Canine leukocyte adhesion deficiency (CLAD) is an inherited blood disorder affecting Irish Setters and German Shepherd Dogs. The disease results from breed-specific mutations in genes that are integral to platelet and blood cell activity. Affected dogs have abnormal blood clotting and immune system functions. Affected German Shepherd Dogs and Irish Setters may present with lameness, recurrent skin infections including pyoderma (pus filled skin infections), furunculosis (boils) and ulceration, osteomyelitis (bone infections) and gingivitis. Additionally, Irish Setter pups may exhibit omphalophlebitis (umbilical vein infection), generalized lymphadenopathy (swollen or inflamed lymph nodes), and a failure to gain weight. Although some dogs can live for years with this condition, most affected dogs die early from severe infection or bleeding from an accidental injury, or during a surgical procedure. Veterinarians should be informed of affected dogs prior to any surgical procedures.
CLAD-Type I (reported as CLADis) in Irish Setters results from a single nucleotide change (c.107G>C) in the beta-2 integrin gene (ITGB2). The disease is inherited in an autosomal recessive fashion, which means that males and females are equally affected and that two copies of the defective gene are needed to cause CLAD. Dogs with one normal and one affected gene (carriers) are normal and show no signs of disease.
Testing for CLAD assists clinicians with diagnosis of CLAD and helps breeders identify carriers among breeding stock to avoid producing affected dogs. Matings between carriers are expected to produce 25% of affected puppies.
Kijas, J.M., Bauer, T.R. Jr., Gäfvert, S., Marklund, S., Trowald-Wigh, G., Johannisson, A., Hedhammar, A., Binns, M., Juneja, R.K., Hickstein, D.D., & Andersson, L. (1999). A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics, 61, 101–110. doi: 10.1006/geno.1999.5948
Boudreaux, M.K., Wardrop, K.J., Kiklevich, V., Felsburg, P., & Snekvik, K. (2010). A mutation in the canine Kindlin-3 gene associated with increased bleeding risk and susceptibility to infections. Journal of Thrombosis and Haemostasis, 103(2), 475-477. doi: 10.1160/TH09-09-0571