Epidermolysis bullosa, junctional, ITGA6-related

Gene: ITGA6

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, ITGA6 gene (splicing error) ; c.2160+1G>T, p.Ile657Met frameshift STOP 1), exon15, chromosome 2.

Breed: Charolais

Medical system: Dermal

Age of onset of symptoms: At birth.

Junctional epidermolysis bullosa in Charolais cows is a genetic disease characterized by congenital skin fragility with mechanically induced blistering of the skin and mucous membranes. Clinical signs appear from birth and include skin erosion and ulceration in areas of skin folds and friction such as at the base of the neck, ears, limb tips, muzzle, and tongue. Abnormal growth or development of the hooves may lead to hoof decay. Additionally, affected calves may have minor malformations of the tips of the ear flaps. Young animals with junctional epidermolysis bullosa are normally euthanized for humane reasons, as there are no curative treatments available for this genetic disease.

DNA studies identified a mutation in the ITGA6 gene as one cause of the disease phenotype. The ITGA6 gene codes for the A6 subunit of integrin proteins; integrins are transmembrane proteins that are essential for attachment epithelial cells to the basement membrane via hemidesmosomes.

Note that the A6 subunit of integrins associates with the beta 4 subunit, coded for by the ITGB4 gene. A mutation in the ITGB4 gene is another cause of epidermolysis bullosa in the cow.