A Genetic Mutation Causes a Rare Skin Disease in Dogs

August 4, 2017
JoAnna Pendergrass, DVM

Dr. Pendergrass received her DVM degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory Universitys Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner ofJPen Communications, a medical communications company.

Researchers have identified a genetic mutation responsible for recessive dystrophic epidermolysis bullosa in Central Asian Shepherd dogs.

In Central Asian Shepherd (CAS) dogs, a pathological variant of the COL7A1 gene causes a rare and serious skin disease called recessive dystrophic epidermolysis bullosa (RDEB), according to a study recently published in PLoS One.

Identifying this gene variant, the study’s researchers believe, “enables an efficient identification of the carrier dogs and subsequent eradication of this serious disease through revised breeding programs.”

Epidermolysis bullosa (EB) is a rare, heritable skin disease affecting humans, dogs, and other species. It is characterized by cleavage at the dermo-epidermal junction, leading to fragility of the skin and mucus membranes, blisters, and skin erosions. EB has several subtypes, such as RDEB, differentiated by level of cleavage at the junction (eg, within the lamina lucida, below the lamina densa).


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To date, 4 of the 19 recessive or dominant EB genes identified in humans—including COL7A1, which codes for the protein regulating collagen VII assemblyare reportedly associated with canine EB. Mutations of these 19 genes disrupt normal development of basement membrane structural proteins. Previous studies have reported COL7A1 mutations in human dystrophic EB. The current study reported the cases of 2 CAS puppies with severe RDEB.

Case Presentation

From a litter of 8 CAS puppies born to healthy parents, 2 littermates presented with severe skin and oral mucosa lesions soon after birth. The puppies were euthanized due to poor prognosis and were then necropsied.

Following necropsy, samples were processed for histological examination. All samples were stained with hematoxylin and eosin. Skin samples underwent periodic acid-Schiff (PAS) staining to identify dermo-epidermal cleavage. To detect basement membrane collagen VII, immunohistochemistry (IHC) was performed with a COL7A1 antibody on skin samples from the affected CAS puppies and age-matched puppies from different breeds (‘control’ puppies) that had died of other causes.

Whole genome sequencing was performed on 1 of the affected CAS puppies. Also, blood samples were collected from the affected puppies’ healthy littermates and parents, as well as other non-EB CAS dogs.

Case Results

Necropsy and Histology

Vesicles, bullae, and ulcers were observed on various body parts, including the oral and oropharyngeal mucosa, footpads, and ventral abdomen. Several histological findings were noted, including:

  • Dermo-epidermal cleavage
  • Inflammatory cells and necrotic debris in the clefts
  • Variably-sized vacuoles at the basement membrane
  • PAS-positive material on the top and bottom of the clefts, suggesting a basement membrane

Other sampled tissues (internal organs and brain) did not demonstrate EB-related pathologic changes.

Whole genome sequencing

Whole genome sequencing identified a COL7A1 variant in one of the affected CAS puppies. This variant resulted in a premature stop codon in the gene, likely leading to production of non-functional COL7A1 protein and a subsequent lack of collagen VII assembly in the basement membrane.

Because the puppies’ parents were healthy, researchers suspected a recessive mode of disease inheritance. To confirm this suspicion, they genotyped the COL7A1 variant in the other affected puppy, along with the puppies’ parents, healthy littermates, and other non-EB CAS dogs. Genotyping results demonstrated that the parents and healthy littermates were heterozygous carriers and the 2 affected puppies were homozygous recessive for the COL7A1 mutation.


IHC staining for collagen VII was positive in the control puppies’ skin samples and negative in the affected CAS puppies’ skin samples. This finding, wrote the researchers, “demonstrates the absence of functional COL7A1 in the affected dogs.”

Future Implications

Although no treatment exists for EB, researchers believe that gene therapy to restore epithelial collagen VII production is a potential treatment option for RDEB.

Dr. JoAnna Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.