LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa.

Kiener, Sarah; Laprais, Aurore; Mauldin, Elizabeth A; Jagannathan, Vidya; Olivry, Thierry; Leeb, Tosso (2020). LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa. Genes, 11(9) MDPI, Molecular Diversity Preservation International 10.3390/genes11091055

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In a highly inbred Australian Shepherd litter, three of the five puppies developed widespread ulcers of the skin, footpads, and oral mucosa within the first weeks of life. Histopathological examinations demonstrated clefting of the epidermis from the underlying dermis within or just below the basement membrane, which led to a tentative diagnosis of junctional epidermolysis bullosa (JEB) with autosomal recessive inheritance. Endoscopy in one affected dog also demonstrated separation between the epithelium and underlying tissue in the gastrointestinal tract. As a result of the severity of the clinical signs, all three dogs had to be euthanized. We sequenced the genome of one affected puppy and compared the data to 73 control genomes. A search for private variants in 37 known candidate genes for skin fragility phenotypes revealed a single protein-changing variant, LAMB3:c.1174T>C, or p.Cys392Arg. The variant was predicted to change a conserved cysteine in the laminin β3 subunit of the heterotrimeric laminin-322, which mediates the binding of the epidermal basement membrane to the underlying dermis. Loss-of-function variants in the human LAMB3 gene lead to recessive forms of JEB. We confirmed the expected co-segregation of the genotypes in the Australian Shepherd family. The mutant allele was homozygous in two genotyped cases and heterozygous in three non-affected close relatives. It was not found in 242 other controls from the Australian Shepherd breed, nor in more than 600 other controls. These data suggest that LAMB3:c.1174T>C represents the causative variant. To the best of our knowledge, this study represents the first report of a LAMB3-related JEB in domestic animals.

Item Type:

Journal Article (Original Article)


05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Kiener, Sarah, Jagannathan, Vidya, Leeb, Tosso


500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




MDPI, Molecular Diversity Preservation International




Tosso Leeb

Date Deposited:

11 Sep 2020 14:11

Last Modified:

05 Dec 2022 15:40

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Canis lupus familiaris dermatology dog genodermatosis laminin precision medicine skin wgs whole genome sequence




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