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Ectodermal Dysplasia Chesepeake Bay Retriever Type
| Acronym: | ED-SFS |
| Gene: | PKP1 |
| Mutation: | c.202+1G>C |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Ectodermal Dysplasia Chesapeake Bay Retriever Type or Ectodermal Dysplasia-Skin Fragility Syndrome (ED/SFS) in Chesapeake Bay Retriever is an inherited skin disorder affecting the Chesapeake Bay Retrievers. It is associated with epidermal cell-cell separation, a condition known as acantholysis. Congenital and hereditary disorders of skin adhesion are gathered in a group of disorders known as epidermolysis bullosa (EB). ED/SFS is known to affect humans and dogs, and it was first time described in 1997 in a human patient as an inherited skin disorder, or genodermatosis. ED/SFS in Chesapeake Bay Retriever was the first hereditary epidermolysis bullosa described in animal species. Mutations in the gene encoding protein plakophilin-1 (PKP1) have been associated with Ectodermal Dysplasia / Skin Fragility Syndrome. Protein plakophilin-1 interacts with the protein desmoplakin, a component of desmosome that has an important role in maintaining the structural integrity of neighboring cells.
The first clinical signs are noticed already at birth. Affected cubs exhibit fragile and pale skin and diffuse inflammatory skin disease, erythroderma. These signs appear in areas of friction or trauma. Common symptoms are also chronic perioral inflammation with cracking, known as cheilitis, and abnormal thickening of footpads, palmoplantar keratodermas, with fissures. Affected dogs exhibit hair abnormalities such as partial hypotrichosis, complete hairlessness, and woolly hair as well as nail dystrophies. Growth delay is present. Light microscopy examination reveals a widening of intercellular space with dissociation between epidermal cells in the superficial epidermal layers. This widening of intercellular space results in epithelial sloughing, or erosions. Epidermal cell-cell separation, or acantholysis, is associated with the aggregation of the keratin cytoskeleton, a condition known as dyskeratosis. Acantholysis decreases with the aging of the dog, but the epidermis becomes hyperplastic and hyperkeratotic. Transmission electron microscopy examination reveals a reduced number of hypoplastic desmosomes.
Ectodermal Dysplasia Chesapeake Bay Retriever Type (ED/SFS) is caused by a splice mutation of the PKP1 gene encoding for protein plakophilin-1 (PKP1). The mutation causes a premature stop codon, resulting in truncated PKP1 protein. Such PKP1 results in incorrect recruitment of desmoplakin and consequentially dysfunctional desmosome formation and structure. ED/SFS in Chesapeake Bay Retriever is inherited as an autosomal recessive disorder. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of ED/SFS. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Olivry T, Linder KE, Wang P, Bizikova P, Bernstein JA, et al. (2012) Deficient Plakophilin-1 Expression Due to a Mutation in PKP1 Causes Ectodermal Dysplasia-Skin Fragility Syndrome in Chesapeake Bay Retriever Dogs. PLoS ONE 7(2): e32072. doi:10.1371/journal.pone.0032072