In other species: horse , taurine cattle

Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 226700 (trait) , 600805 (gene) , 245660 (trait) , 226650 (trait)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2005

Cross-species summary: Congenital blistering skin disease characterized by separation of the lamina lucida of the basement membrane zone. Blisters often occur in and around the mouth and on the limbs, leading in the latter case to separation of the hoof or nail from the corium (dermis).

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Capt et al. (2005) were able to report that "The condition is associated with reduced expression of laminin 5 caused by a homozygous insertion (4818+207ins6.5 kb) of repetitive satellite DNA within intron 35 of the gene (LAMA3) for the laminin alpha3 chain. The intronic mutation interferes with maturation of the alpha3 pre-messenger RNA resulting in the coexpression of a transcript with a 227 nucleotide insertion and a wild-type mRNA that encodes scant amounts of the alpha3 polypeptide." Herrmann et al. (2021): “Whole genome sequencing (WGS) of one affected [Australian cattle dog cross-bred] puppy was compared to a database of 522 dogs of 55 different breeds for variant analysis. … The WGS revealed a novel missense variant in the laminin α3-chain XP_537297.2p(Asp2867Val). … Sanger sequencing of one additional affected and one unaffected sibling confirmed the variant.”

Clinical features: Herrmann et al. (2021): "Five of eight puppies in an Australian cattle dog cross-bred litter showed signs of skin fragility. Three were stillborn and one died at one month of age. The two surviving puppies were presented with blistering skin disease and severe respiratory distress."

Pathology: Herrmann et al. (2021): “Histopathological results revealed subepidermal clefts and electron microscopy confirmed the split in the lamina lucida. Post-mortem examination documented extensive pharyngeal and laryngeal lesions with granulation tissue and fibrinous exudate obscuring the airway.”

Breeds: Australian Cattle Dog X, German Pointer (Dog) (VBO_0200574).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).

Associated gene: