Leukocyte adhesion deficiency (LAD), type 1 (ITGB2-linked)

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: Deletion, ITGB2 gene (splicing error): c.46_58 + 11del (24 nt), deletion of exon2, Chr.21.

Medical system: Immune

Breeds: Domestic Cat

Age of onset of symptoms: Soon after birth

Leucocyte adhesion deficiency (LAD), also known as CD18 deficiency, is an autosomal recessive disease of the immune system seen in several species including the dog (CLAD), cattle (BLAD) and humans.  Mutations in the ITGB2 gene result in the production of a defective integrin b2 subunit (CD18) adhesion protein on the surface of neutrophils, resulting in an inability of blood leucocytes to pass from the blood into tissues to combat bacterial infections.  LAD was diagnosed in a single domestic cat with recurring bacterial infections and poor response to antibiotics.  The cat showed increased neutrophile blood counts but neutrophils lacked CD18 expression. Molecular studies identified a deletion within the ITGB2 gene that removed exon2, and further that the affected cat was homozygous for the mutation.  Screening of an additional 93 cats for the same mutation failed to reveal carrier animals.  These findings suggest that this mutation is rare within the general domestic cat population, and that feline LAD caused by this mutation is not of general clinical concern. However, the fact that the affected cat was homozygous for the mutation may warrant wider screening trials.

References:

OMIA link: [0595-9685]

Lyons LA. (2024) Genetic testing: practical dos and don’ts for cats.  J Feline medicine and surgery 26:1-13.  [pm/39648935]

Bauer TR, Pratt SM, Palena CM, et al. (2017) Feline leukocyte adhesion (CD18) deficiency caused by a deletion in the integrin β2 (ITGB2) gene. Vet Clin Pathol 46:391-400.  [pm/28750142]

Contributed by:   Zoe Gauthier and Juliette Plante, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).