Thrombasthenia, Glanzmann’s (ITGA2B-linked)

Gene: ITGA2B

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.

Mutations:

Mutation 1: Deletion, ITGA2B gene: c.1839 del.C, p.(Pro613 frameshift), exon18, Chr.E1

Mutation 2: Insertion, ITGA2B gene: c.1839_1840 ins.CC, p.(E614 frameshift), exon18, Chr.E1

Medical system: Blood

Breeds: Domestic Cat

Age of onset of symptoms: In the adult cat or after a surgical procedure.

Thrombasthenia, also referred to as Glanzmann thrombasthenia is a genetic disease of platelets that results in a difficulty in clot formation (coagulopathy) and a prolonged bleeding time.  Platelets have low to absent levels of the product of the ITGA2B gene, an integrin protein on the platelet membrane that is necessary for proper platelet crosslinking via fibrinogen and von Willebrand clotting factors.

Thrombasthenia is rarely seen in cats but has been recently diagnosed at the clinical and molecular levels in two separate cases in domestic cats.  In the first case, prolonged bleeding and hematoma formation within the bladder was observed following a cystocentesis procedure.  In the second case, the cat was examined clinically for recurring breathing difficulties.  In both cases, blood analysis revealed reduced platelet counts (thrombocytopenia).  Whole genome sequencing identified distinct mutations, one a deletion and the other an insertion, at the same site within the ITGA2A gene.  The mutations were not observed in publicly available cat genomic data banks.

Mutations within the ITGA2B gene are a known cause of Glanzmann thrombasthenia in dogs.

References:

OMIA link: [1000-9685]

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

Rivas VN, Tan AWK, Shaverdian M, et al. (2024) A novel ITGA2B double cytosine frameshift variant (c.1986_1987insCC) leads to Glanzmann’s thrombasthenia in a cat. J Vet Intern Med 38:1408-1417.  [pm/38426552]

Haginoya S, Thomovsky EJ, Johnson PA, Brooks AC. (2023) Clinical assessment of primary hemostasis: A review. Top Companion Anim Med 56-57:S1938-9736(23)00058-2:100818.  [pm/37673175]

Li RHL, Ontiveros E, Nguyen N, et al. (2020) Precision medicine identifies a pathogenic variant of the ITGA2B gene responsible for Glanzmann’s thrombasthenia in a cat. J Vet Intern Med 34:2438-2446.  [pm/32935881]

With contributions by:   Erika Lacerte and Alexia Petitclerc, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).