A stop-gain in the Laminin A3 (LAMA3) gene causes recessive Junctional Epidermolysis Bullosa in Belgian Blue Cattle.. Epidermolysis_Bullosa_Belgian_Blue

Four newborn purebred Belgian Blue calves presenting a severe form of epidermolysis bullosa were recently referred to our heredo-surveillance platform. SNP array genotyping followed by autozygosity mapping located the causative gene in a 8.3 Mb interval on bovine chromosome 24. Combining information from (i) whole-genome sequencing of an affected calf, (ii) transcriptomic data from a panel of tissues and (iii) a list of functionally ranked positional candidates, pinpointed a private G to A nucleotide substitution in the LAMA3 gene. It creates a premature stop codon (p.R2609X) in exon 60, truncating 22% of the corresponding protein. The LAMA3 gene encodes the 3 subunit of the heterotrimeric laminin-332, a key constituent of the lamina lucida that is part of the skin basement membrane connecting epidermis and dermis layers. Homozygous loss-of-function mutations in this gene are known to cause severe junctional epidermolysis bullosa in human, mice, horse, sheep and dog. Overall our data strongly support the causality of the identified gene and mutation.