Canine Leucocyte Adhesion Deficiency (CLAD) , Type1

 

Gene: ITGB2

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, ITGB2 gene; c.107 G>C, p.(C36S), exon4

Medical systems: Blood, immune

Breeds: Irish Red and White Setter, Irish Setter

Age of onset of symptoms: At birth, death by 6 months of age

Canine Leukocyte Adhesion Deficiency (CLAD) in the Irish Setter and the Irish Red and White Setter is an autosomal recessive genetic disease affecting the white blood cells of the immune system.  CLAD is caused by a mutation in a protein (integrin b2 subunit, CD18) on the surface of white blood cells (leukocytes).  This mutation blocks the ability of leukocytes to interact with other cells and with the extracellular matrix which severely reduces the immune system’s ability to fight infections.  From birth, affected puppies are smaller than their normal littermates and will not develop as well. The affected puppies will suffer from recurrent infections, poor wound healing, lameness and low body weight.  They will often have severe skin infections, gingivitis, fever and infection of the umbilical vein (omphalophlebitis).  Untreated, affected puppies will die within 6 months of age.  Euthanasia of affected puppies is the humanitarian option.

 

References:

OMIA link: [0595-9615]

Pfeiffer I, Brenig B. (2005) Frequency of the Canine Leucocyte Adhesion Deficiency (CLAD) mutation among Irish Red Setters in Germany . J Anim Breed Genet. 122(2):140-2. [pubmed/16130481]

Debenham SL, Millington A, Kijas J, et al. (2002) Canine leucocyte adhesion deficiency in Irish red and white setters. Journal of Small Animal Practice 43:74-75.  [pubmed/11873952]

Kijas JM, Bauer Jr. TR, Gafvert S, Marklund S, et al. (1999) A Missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics. 61(1):101-7. [pubmed/10512685]

Renshaw HW, Davis WC. (1979) Canine granulocytopathy syndrome: an inherited disorder of leukocyte function. Am J Pathol. 95(3):731-44. [pubmed/453331]

 

Contributed by: Emily Morgan, Class of 2020, Faculty of Veterinary Medicine, University of Montreal.