A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.

[dystrophic epidermolysis bullosa]

We identified a congenital mechanobullous skin disorder in six calves on a single farm of an endangered German cattle breed in 2010 . The condition presented as a large loss of skin distal to the fetlocks and at the mucosa of the muzzle . All affected calves were euthanized on humane grounds due to the severity , extent and progression of the skin and oral lesions . Examination of skin samples under light microscopy revealed detachment of the epidermis from the dermis at the level of the dermo epidermal junction , leading to the diagnosis of a subepidermal bullous dermatosis such as epidermolysis bullosa . The pedigree was consistent with monogenic autosomal recessive inheritance . We localized the causative mutation to an 18 Mb interval on chromosome 22 by homozygosity mapping . The COL 7 A 1 gene encoding collagen type VII alpha 1 is located within this interval and COL 7 A 1 mutations have been shown to cause inherited dystrophic epidermolysis bullosa (DEB ) in humans . A SNP in the bovine COL 7 A 1 exon 49 (c .4756 C >T ) was perfectly associated with the observed disease . The homozygous mutant T /T genotype was exclusively present in affected calves and their parents were heterozygous C /T confirming the assumed recessive mode of inheritance . All known cases and genotyped carriers were related to a single cow , which is supposed to be the founder animal . The mutant T allele was absent in 63 animals from 24 cattle breeds . The identified mutation causes a premature stop codon which leads to a truncated protein representing a complete loss of COL 7 A 1 function (p .R 1586 *). We thus have identified a candidate causative mutation for this genetic disease using only three cases to unravel its molecular basis . Selection against this mutation can now be used to eliminate the mutant allele from the Rotes Höhenvieh breed .