UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Canine Leukocyte Adhesion Deficiency (CLAD or LAD)

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). CLAD-Type III (reported as CLADgs) in German Shepherd Dogs results from a 12bp insertion (c.1358_1359insAAGACGGCTGCC) in fermitin family member 3 gene (FERMT3).  In both cases, 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.
The Veterinary Genetics Laboratory offers genetic tests for CLAD. Test results assist veterinarians with diagnosis of CLAD and help breeders identify carriers among breeding stock to avoid producing affected dogs. Matings between carriers are expected to produce 25% of affected puppies.

Testing is recommended for: German Shepherd Dog, Irish Setter

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Allow 5-10 business days for results.

Results reported as:

N/N

Normal - no copies of the CLAD mutation

N/CLAD*

Carrier - 1 copy of the CLAD mutation

CLAD/CLAD*

Affected - 2 copies of the CLAD mutation

* Report will specify CLADis or CLADgs, according to breed

References:

Boudreaux MK, Wardrop KJ, Kiklevich V, Felsburg P, Snekvik K. (2010) A mutation in the canine Kindlin-3 gene associated with increased bleeding risk and susceptibility to infections. Thromb Haemost. 103(2):475-477.


Kijas JM, Bauer TR Jr, Gäfvert S, Marklund S, Trowald-Wigh G, Johannisson A, Hedhammar A, Binns M, Juneja RK, Hickstein DD, Andersson L. (1999) A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics 61, 101–110.

 
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